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B S Allen

Publications and source records attributed to B S Allen.

At least 37 records · Page 2Linked to original sources
PubMed1998

The importance of cardioplegic infusion pressure in neonatal myocardial protection.

BACKGROUND: Cardioplegia infusion pressure is usually not directly monitored during neonatal heart operations. We hypothesize that the immature newborn heart may be damaged by even moderate elevation of cardioplegic infusion pressure, which in the absence of direct aortic monitoring may occur without the surgeon's knowledge. METHODS: Twenty neonatal piglets received cardiopulmonary bypass and the heart was protected for 70 minutes with multidose blood cardioplegia infused at an aortic root pressure of 30 to 50 mm Hg (low pressure) or 80 to 100 mm Hg (high pressure). Group 1 (n = 5, low pressure), and group 2 (n = 5, high pressure) were uninjured (nonhypoxic) hearts. Group 3 (n = 5, low pressure) and group 4 (n = 5, high pressure) first underwent 60 minutes of ventilator hypoxia (FiO2 8% to 10%) before initiating cardiopulmonary bypass to produce a clinically relevant hypoxic stress before cardiac arrest. Function was assessed using pressure volume loops (expressed as a percentage of control), and coronary vascular resistance was measured with each cardioplegic infusion. RESULTS: In nonhypoxic (uninjured) hearts (groups 1 and 2) cardioplegic infusion pressure did not significantly affect systolic function (end systolic elastance, 104% versus 96%), preload recruitable stroke work (102% versus 96%) diastolic compliance (152% versus 156%), or coronary vascular resistance but did raise myocardial water (78.9% versus 80.1%; p < 0.01). Conversely, if the cardioplegic solution was infused at even a slightly higher pressure in hypoxic hearts (group 4), there was deterioration of systolic function (end systolic elastance, 28% versus 106%) (p < 0.001) and preload recruitable stroke work (31% versus 103%; p < 0.001), rise in diastolic stiffness (274% versus 153%; p < 0.001), greater myocardial edema (80.5% versus 79.6%), and marked increase in coronary vascular resistance (p < 0.001) compared to hypoxic hearts given cardioplegia at low infusion pressures (group 3), which preserved function. CONCLUSIONS: Hypoxic neonatal hearts are very sensitive to cardioplegic infusion pressures, such that even moderate elevations cause significant damage resulting in myocardial depression and vascular dysfunction. This damage is avoided by using low infusion pressures. Because small differences in infusion pressure may be difficult to determine without a direct aortic measurement, we believe it is imperative that surgeons directly monitor cardioplegia infusion pressure, especially in cyanotic patients.

Animals↗
PubMed1998

Controlled reperfusion after lung ischemia: implications for improved function after lung transplantation.

OBJECTIVES: Despite improvements in organ preservation, reperfusion injury remains a major source of morbidity and mortality after lung transplantation. This pilot study was designed to investigate the effects of controlled reperfusion after lung ischemia. METHODS: Twenty adult pigs underwent 2 hours of warm lung ischemia by crossclamping the left bronchus and pulmonary artery. In five (group 1), the clamp was simply removed at the end of ischemia (uncontrolled reperfusion). The 15 other pigs underwent modified reperfusion using blood from the femoral artery to perfuse the lung through the pulmonary artery (pressure 40 to 50 mm Hg) for 10 minutes before removing the pulmonary artery clamp. In five (group 2), the blood was mixed with crystalloid, resulting in a substrate-enriched, hypocalcemic, hyperosmolar, alkaline solution. In five (group 3), the blood was circulated through a leukocyte-depleting filter, and the last five (group 4) underwent reperfusion with both a modified solution and white blood cell filter. Lung function was assessed 60 minutes after reperfusion, and biopsy specimens were taken. RESULTS: Controlled reperfusion with both a white blood cell filter and modified solution (group 4) completely eliminated the reperfusion injury that occurred with uncontrolled reperfusion (group 1), resulting in complete preservation of compliance (98% +/- 1% vs 77% +/- 1%; p < 0.001, and arterial/alveolar ratio (97% +/- 2% vs 27% +/- 2%; p < 0.001); no increase in pulmonary vascular resistance (106% +/- 1% vs 198% +/- 1%; p < 0.001); lowered tissue edema (82.1% +/- 0.4% vs 84.3% +/- 0.2%; p < 0.001), and myeloperoxidase activity (0.18 +/- 0.02 vs 0.35 +/- 0.02 deltaOD/min/mg protein; p < 0.001). In contrast, using either a white blood cell filter or modified solution separately improved but did not avoid the reperfusion injury, resulting in pulmonary function and tissue edema levels that were intermediate between group 1 (uncontrolled reperfusion) and group 4 (white blood cell filter and modified solution). CONCLUSION: After 2 hours of warm pulmonary ischemia, (1) a severe lung injury occurs after uncontrolled reperfusion, (2) controlled reperfusion with either a modified reperfusion solution or white blood cell filter limits, but does not avoid, a lung reperfusion injury, (3) reperfusion using both a modified reperfusate and white blood cell filter results in complete preservation of pulmonary function. We therefore believe surgeons should control the reperfusate after lung transplantation to improve postoperative pulmonary function.

Animals↗
PubMed1998

Prevention of ischemic damage using controlled limb reperfusion.

Following prolonged limb ischemia, a reperfusion injury may occur with the reintroduction of unmodified blood, resulting in tissue loss and, in severe cases, limb loss. We have shown that the reperfusion injury in the heart can be minimized by using controlled reperfusion with a substrate-enriched cardioplegia solution prior to restoring normal blood flow. This article describes two clinical cases in which we used controlled reperfusion in an ischemic limb to prevent limb loss. It demonstrates that a controlled, substrate-enhanced, hypocalcemic, leukodepleted, modified blood reperfusate solution can minimize limb reperfusion damage and improve functional recovery. This preliminary experience is presented to familiarize surgeons with this form of treatment and to describe the solutions and method of administration that can be used to avoid the devastating complications of severe limb ischemia.

Aged↗
PubMed1997

Lipoxygenase metabolism is required for interleukin-3 dependent proliferation and cell cycle progression of the human M-07e cell line.

The cell line M-07e requires either Interleukin-3 (IL-3) or granulocyte-macrophage colony stimulating factor (GM-CSF) for proliferation in vitro. Cells deprived of growth factor for up to 48 hours remain viable but no longer divide. The growth-factor-deprived M-07e cells begin to divide within 48 hours of reexposure to IL-3. Flow cytometric analysis of M-07e cells labeled with hypotonic propidium iodide demonstrates that the percentage of cells undergoing DNA synthesis decreases from 24%, in a log phase population of IL-3 stimulated cells, to 1% when cells are deprived of IL-3 for 24 hours. IL-3-deprived cells accumulate predominantly in a flow cytometry peak representative of G0/G1. DNA synthetic activity, as determined by tritiated thymidine uptake and flow cytometry, resumes between 12 and 18 hours after reexposure to IL-3, reaching a peak of up to 40% by 24 hours and returning to log phase levels by 72 hours. Prior to initiation of DNA synthesis, increases are seen in mRNA levels for five-lipoxygenase-activating protein (FLAP). Following reexposure to IL-3, a rapid time-dependent biosynthesis of leukotriene D4 (LTD4) is induced by M-07e cells. When IL-3 is added in the presence of any of three lipoxygenase inhibitors tested (Piriprost, caffeic acid, nordihydroguiaretic acid) or FLAP inhibitor, MK-886, there is dose-dependent inhibition of the resumption of proliferation and of DNA synthesis. Flow cytometric cell cycle analysis demonstrates that the inhibited cells remain in the G0/G1 population and do not progress through the cell cycle. These results are consistent with our previous observation that an intact lipoxygenase pathway is necessary for hematopoietic growth-factor-stimulated colony formation of normal bone marrow myeloid progenitors and suggest that the induction of a lipoxygenase metabolite or metabolites is necessary for myeloid cells to progress through the cell cycle when stimulated by a hematopoietic growth factor.

5-Lipoxygenase-Activating Proteins↗
PubMed1997

Detrimental effects of cardiopulmonary bypass in cyanotic infants: preventing the reoxygenation injury.

BACKGROUND: Recent experimental studies have shown that acute hypoxia followed by abrupt reoxygenation using cardiopulmonary bypass (CPB) results in an unintended injury mediated by oxygen free radicals, which can be modified by initiating CPB at a lower fraction of inspired oxygen (FiO2) or by leukocyte filtration. However, the clinical relevance of these experimental studies has been questioned because chronic hypoxia may allow compensatory changes to occur. METHODS: Seven acyanotic infants had CPB initiated at an FiO2 of 1.0. Of 21 cyanotic infants, 7 (group 1) had CPB initiated at an FiO2 of 1.0, 6 (group 2) at an FiO2 of 0.21, and 8 (group 3) underwent CPB using leukocyte filtration. Biopsy of right atrial tissue was performed before and 10 to 20 minutes after the initiation of CPB. The tissue was incubated in 4-mmol/L t-butylhydroperoxide (a strong oxidant), and the malondialdehyde (MDA) level was measured to determine the antioxidant reserve capacity. The more MDA produced, the greater was the depletion of tissue antioxidants secondary to oxygen free radical formation during reoxygenation. RESULTS: There was no difference in the prebypass antioxidant reserve capacity between cyanotic and acyanotic hearts (492 +/- 72 versus 439 +/- 44 nmol MDA/g protein). However, after the initiation of CPB without leukocyte filtration, MDA production rose markedly in the cyanotic (groups 1 and 2) as compared with the acyanotic hearts (322% versus 40%; p < 0.05), indicating a depletion of antioxidants. In cyanotic hearts, initiating CPB at an FiO2 of 1.0 (group 1) resulted in increased MDA production (407% versus 227%) as compared with hearts in which CPB was initiated at an FiO2 of 0.21 (group 2), indicating a greater generation of oxygen free radicals in group 1. Conversely, there was only a minimal increase in MDA production in 8 of the 21 infants (group 3) in whom white blood cells were effectively filtered (19% versus 322%; p < 0.05). CONCLUSIONS: First, increased amounts of oxygen free radicals are generated in cyanotic infants with the initiation of CPB. Second, this production is reduced by initiating CPB at an FiO2 of 0.21 or by effectively filtering white blood cells. Third, these changes parallel those seen in the acute experimental model, validating its use for future study.

Antioxidants↗
PubMed1997

The relationship between calcium and magnesium in pediatric myocardial protection.

OBJECTIVE: We previously demonstrated that calcium can be harmful to the hypoxic neonatal heart. Despite the fact that magnesium inhibits membrane transport of calcium, few studies have examined whether magnesium can prevent the deleterious effects of calcium in cardioplegic solutions. METHODS: Twenty neonatal piglets (5 to 18 days old) underwent 60 minutes of ventilator hypoxia (inspired oxygen fraction 8% to 10%) followed by reoxygenation with the use of cardiopulmonary bypass before cardioplegic arrest to produce a clinically relevant hypoxic "stress" injury. The aorta was then crossclamped for 70 minutes with multidose blood cardioplegia. Ten piglets received a hypocalcemic (0.2 to 0.4 mmol/L) cardioplegic solution without (group 1, n = 5) or with magnesium (10 mEq/L) (group II, n = 5) supplementation. Ten other piglets were protected with a normocalcemic (1.0 to 1.2 mmol/L) cardioplegic solution without (group III, n = 5) or with magnesium (group IV, n = 5). Myocardial function was assessed by means of pressure volume loops and expressed as a percentage of control. Coronary vascular resistance was assessed during each cardioplegic infusion. RESULTS: Adding magnesium to a hypocalcemic cardioplegic solution (groups I and II) had no effect: Both groups had complete preservation of postbypass systolic function (end-systolic elastance 101% vs 104%) and preload recruitable stroke work (101% vs 102%), minimal increase in diastolic stiffness (159% vs 153%), and no difference in myocardial tissue edema (78.8% vs 78.9%) or coronary vascular resistance. Conversely, when a normocalcemic cardioplegic solution was administered without magnesium supplementation (group III), the results were markedly poorer than results obtained with magnesium supplementation (group IV). Without magnesium, there was a marked reduction in postbypass systolic function (end-systolic elastance 49% vs 101%; p < 0.05), increased diastolic stiffness (276% vs 162%; p < 0.05), decreased preload recruitable stroke work (53% vs 102%; p < 0.05), increased myocardial tissue edema (80.0% vs 78.9%; p < 0.05), and a rise in coronary vascular resistance (p < 0.05). Magnesium supplementation of the normocalcemic cardioplegic solution, by contrast, resulted in complete functional recovery. CONCLUSIONS: This study demonstrates that (1) magnesium does not alter the cardioprotective effects of a hypocalcemic cardioplegic solution, (2) a normocalcemic cardioplegic solution is detrimental to neonatal myocardium subjected to a previous hypoxic stress, and (3) magnesium supplementation of normocalcemic cardioplegic solutions prevents the deleterious effects of calcium.

Animals↗
PubMed1997

Myocardial protection in normal and hypoxically stressed neonatal hearts: the superiority of blood versus crystalloid cardioplegia.

OBJECTIVES: Blood cardioplegia predominates in the adult because it provides superior myocardial protection, especially in the ischemically stressed heart. However, the superiority of blood over crystalloid cardioplegia in the pediatric population is unproved. Furthermore, because many pediatric hearts undergo a preoperative stress such as hypoxia, it is important to compare the different methods of protection in both normal and hypoxic hearts. METHODS: Twenty neonatal piglets were supported by cardiopulmonary bypass and subjected to 70 minutes of cardioplegic arrest. Of 10 nonhypoxic hearts, five (group 1) were protected with blood cardioplegia and five (group 2) with crystalloid cardioplegia (St. Thomas' Hospital solution). Ten other piglets underwent 60 minutes of ventilator hypoxia (inspired oxygen concentration 8% to 10%) before cardioplegic arrest. Five (group 3) were then protected with blood cardioplegia and the other five (group 4) with crystalloid cardioplegia. Myocardial function was assessed by means of pressure volume loops and expressed as a percentage of control. Coronary vascular resistance was measured with each infusion of cardioplegic solution. RESULTS: No difference was noted between blood (group 1) or crystalloid cardioplegia (group 2) in nonhypoxic hearts regarding systolic function (end-systolic elastance 104% vs 103%), diastolic stiffness (156% vs 159%), preload recruitable stroke work (102% vs 101%), or myocardial tissue edema (78.9% vs 78.9%). Conversely, in hearts subjected to a hypoxic stress, blood cardioplegia (group 3) provided better protection than crystalloid cardioplegia (group 4) by preserving systolic function (end-systolic elastance 106% vs 40%; p < 0.05) and preload recruitable stroke work (103% vs 40%; p < 0.05); reducing diastolic stiffness (153% vs 240%; p < 0.05) and myocardial tissue edema (79.6% vs 80.1%); and preserving vascular function, as evidenced by unaltered coronary vascular resistance (p < 0.05). CONCLUSION: This study demonstrates that (1) blood or crystalloid cardioplegia is cardioprotective in hearts not compromised by preoperative hypoxia and (2) blood cardioplegia is superior to crystalloid cardioplegia in hearts subjected to the preoperative stress of acute hypoxia.

Animals↗
PubMed1997

Prevention of the hypoxic reoxygenation injury with the use of a leukocyte-depleting filter.

OBJECTIVES: Recent studies have shown that an injury occurs when the hypoxic heart is suddenly reoxygenated (as occurs with cardiopulmonary bypass), resulting in myocardial depression, impaired oxygenation, and increased pulmonary vascular resistance. We hypothesize that this injury is, in part, due to oxygen-derived radicals produced by activated white cells and may therefore be ameliorated by limiting leukocytes in the bypass circuit. METHODS: Fifteen neonatal piglets underwent 60 minutes of ventilator hypoxia (inspired oxygen fraction 8% to 10%), followed by reoxygenation with cardiopulmonary bypass at an inspired oxygen fraction of 100% for 90 minutes. In nine piglets (group 1) our routine bypass circuit was used with no modifications, and in six piglets (group 2) a leukocyte-depleting filter (Pall BC-1; Pall Biomedical Products Corporation, Glencoe, N.Y.) was inserted in the arterial line to lower the neutrophil count. Six additional piglets underwent 90 minutes of bypass without hypoxia (cardiopulmonary bypass controls). Postbypass myocardial and pulmonary function was assessed by pressure volume loops, arterial/alveolar ratio, and pulmonary vascular resistance index. Results are expressed as a percentage of control. RESULTS: By comparison with group 1 piglets (reoxygenation without a filter), hypoxic piglets undergoing reoxygenation with a leukocyte-depleting filter (group 2) had improved myocardial systolic function (88% vs 52%; p < 0.05), diastolic compliance (175% vs 275%; p < 0.05), and preload recruitable stroke work (91% vs 54%; p < 0.05); had better preservation of the arterial/alveolar ratio (97% vs 74%; p < 0.05); and had less increase in pulmonary vascular resistance (229% vs 391%; p < 0.05). Furthermore, leukocyte filtration prevented adenosine triphosphate depletion or a change in tissue antioxidants. Conversely, unprotected piglets (group 1) exhibited lower levels of adenosine triphosphate and significant loss of tissue antioxidants. Indeed, the results in the leukocyte-filtered piglets (group 2) were nearly identical to those of piglets subjected to bypass without hypoxia (controls). CONCLUSIONS: (1) This study demonstrates that a major component of the injury that occurs when the hypoxic heart is abruptly reoxygenated is caused by oxygen radicals produced by white blood cells; (2) this injury can be prevented by a leukocyte-depleting filter; and (3) avoidance of this injury improves postbypass myocardial and pulmonary function. These data suggest that leukocyte depletion should be used routinely in all children undergoing operations for cyanotic heart disease or extracorporeal membrane oxygenation.

Adenosine Triphosphate↗
PubMed1996

Integrated cardioplegia allows complex valve repairs in all patients.

BACKGROUND: Traditionally, most surgeons have taken adversarial positions with respect to whether cardioplegia should be given warm or cold, antegrade or retrograde, continuous or intermittent. Because each method has weaknesses, myocardial protection is compromised when only one method is employed. It is our contention that an "integrated" approach that combines all of the aforementioned principles will improve myocardial protection, allowing the time needed for complex valve repairs. METHODS: Thirty-four patients (25 undergoing complex mitral valve repairs and 9 undergoing Ross procedures) have undergone complex valve repair since we began using an integrated cardioplegic strategy that incorporates all of the techniques mentioned above and is based on the following principles: (1) Cardioplegia is infused antegrade and retrograde, warm and cold. (2) Surgical precision is optimized by a dry, bloodless field using cold intermittent arrest to limit ischemia when visualization is needed. (3) Continuous blood cardioplegia is used when visualization is not problematic, thereby avoiding unnecessary ischemia. RESULTS: Average age was 46 +/- 4 years (range, 9 to 79 years), and 9 patients (26%) were having reoperations. All mitral patients had severe mitral regurgitation, 52% (13/25) had a preoperative ejection fraction less than 0.40, and 40% (10/25) had pulmonary artery pressures greater than 60 mm Hg. In the Ross patients 33% (3/9) had an ejection fraction less than 0.40, including 2 patients who concomitantly underwent complex mitral valve repair. Despite cross-clamp times of 187 +/- 12 minutes (range, 138 to 267 minutes) in the Ross group and 139 +/- 8 minutes (range, 92 to 218 minutes) in the complex mitral valve repair group with a predicted mortality (Parsonnet) of approximately 10%, no patients died, only 5 (15%) required inotropes, none required intraaortic balloon pumping, only 1 (3%) required antiarrhythmics, and the average postoperative hospital stay was 8 days in the mitral repair group and 5 days in the Ross group. CONCLUSIONS: We believe an integrated approach incorporating the strategies of warm and cold blood cardioplegia, antegrade and retrograde delivery, and continuous and intermittent infusion affords better myocardial protection, avoids unnecessary ischemia, facilitates technical ease of operation, and results in a more stable postoperative course. Integrating these modalities into a comprehensive strategy (instead of relying on one) maximizes each method's strength while minimizing weaknesses, thereby allowing surgeons to perform complex valve repairs safely in all patients.

Aortic Valve Insufficiency↗
PubMed1996

Myocardial protection in normal and hypoxically stressed neonatal hearts: the superiority of hypocalcemic versus normocalcemic blood cardioplegia.

OBJECTIVES: The ideal cardioplegic calcium (Ca+2) concentration in newborns continues to be debated. Most studies examining cardioplegia calcium concentrations have been done with a nonclinical model (i.e., isolated heart preparation), the results of which may not be clinically applicable, and they have not examined the effect of calcium concentration in a clinically relevant stressed (hypoxic) heart. METHODS: Twenty neonatal piglets 5 to 18 days old were placed on cardiopulmonary bypass, and their aortas were crossclamped for 70 minutes with hypocalcemic or normocalcemic multidose blood cardioplegic infusions. Group 1 (n = 5; low Ca+2, 0.2 to 0.4 mmol/L) and group 2 (n = 5; normal Ca+2, 1.0 to 1.3 mmol/L) were nonhypoxic (uninjured) hearts. Ten other piglets were first ventilated at an FiO2 of 8% to 10% (O2 saturation 65% to 70%) for 60 minutes (i.e., causing hypoxia) and then reoxygenated at an FiO2 of 100% with cardiopulmonary bypass, which produces a clinically relevant stress injury. They then underwent cardioplegic arrest (as described above) with a hypocalcemic (n = 5, group 3) or normocalcemic (n = 5, group 4) blood cardioplegic solution. Myocardial function was assessed with pressure volume loops and expressed as a percentage of control values. Coronary vascular resistance was measured during each cardioplegic infusion. All values were reported as the mean +/- standard error. RESULTS: In nonhypoxic hearts (groups 1 and 2), good myocardial protection was achieved at either concentration of cardioplegia calcium, as demonstrated by preservation of postbypass systolic function (104% vs 99% end-systolic elastance), minimally increased diastolic stiffness (152% vs 162%), no difference in myocardial water (78.9% vs 78.9%), and no change in adenosine triphosphate levels or coronary vascular resistance. Low-calcium blood cardioplegia solution repaired the hypoxic reoxygenation injury in stressed hearts (group 3), resulting in no statistical difference in myocardial function, coronary vascular resistance, or adenosine triphosphate levels compared with nonhypoxic hearts (groups 1 and 2). Conversely, when a normocalcemic cardioplegia solution was used in hypoxic hearts (group 4), there was marked reduction in postbypass systolic function (49% +/- 4% end-systolic elastance; p < 0.05), increased diastolic stiffness (276% +/- 9%; p < 0.05), increased myocardial water (80.1% +/- 0.2%; p < 0.05), rise in coronary vascular resistance (p < 0.05), and lower adenosine triphosphate levels compared with groups 1, 2, and 3. CONCLUSIONS: This study demonstrates that, in the clinically relevant, intact animal model, good myocardial protection is independent of cardioplegia calcium concentration in nonhypoxic (noninjured) hearts; hypoxic (stressed) hearts are extremely sensitive to the cardioplegic calcium concentration; and normocalcemic cardioplegia is detrimental to neonatal myocardium subjected to a preoperative hypoxic stress.

Animals↗
PubMed1995

Studies of hypoxemic/reoxygenation injury: without aortic clamping. II. Evidence for reoxygenation damage.

This study tested the hypothesis that the developing heart is susceptible to oxygen-mediated damage after reintroduction of molecular oxygen and that this "unintended" reoxygenation injury causes lipid peroxidation and functional depression that may contribute to perioperative cardiac dysfunction. Among 49 Duroc-Yorkshire piglets (2 to 3 weeks old, 3 to 5 kg) 15 control studies were done without hypoxemia to test the effects of the surgical preparation (n = 10) and 60 minutes of cardiopulmonary bypass (n = 5). Twenty-nine piglets underwent up to 2 hours of ventilator hypoxemia (with inspired oxygen fraction reduced to 6% to 7%) to lower arterial oxygen tension to approximately 25 mm Hg. Five piglets did not undergo reoxygenation to determine alterations caused by hypoxemia alone. Twenty-four others received reoxygenation by either raising ventilator inspired oxygen fraction to 1.0 (n = 12) or instituting cardiopulmonary bypass at oxygen tension 400 mm Hg (n = 12). Ventilator hypoxemia produced sufficient hemodynamic compromise and metabolic acidosis that 18 piglets required premature reoxygenation (78 +/- 12 minutes). To avoid the influence of acidosis and hemodynamic deterioration during ventilator hypoxemia, five others underwent 30 minutes of hypoxemia during cardiopulmonary bypass (circuit primed with blood at oxygen tension 25 mm Hg) and 30 minutes of reoxygenation (oxygen tension 400 mm Hg) during cardiopulmonary bypass. Biochemical markers of oxidant damage included measurement of coronary sinus and myocardial conjugated dienes to determine lipid peroxidation and antioxidant reserve capacity assessed by incubating myocardial tissue in the oxidant t-butylhydroperoxide. Functional recovery was determined by inscribing pressure volume loops to determine end-systolic elastance and Starling curves by volume infusion. No biochemical or functional changes occurred in control piglets. Hypoxemia without reoxygenation did not change plasma levels of conjugated dienes, but lowered antioxidant reserve capacity 24%. Reoxygenation by ventilator caused refractory ventricular arrhythmias in two piglets (17% mortality), raised levels of conjugated dienes 45%, and reduced antioxidant reserve capacity 40% with recovery of 39% of mechanical function in the survivors. Comparable biochemical and functional changes occurred in piglets undergoing ventilator hypoxemia and/or cardiopulmonary bypass hypoxemia and reoxygenation on cardiopulmonary bypass. We conclude that hypoxemia increases vulnerability to reoxygenation damage by reducing antioxidant reserve capacity and that reoxygenation by either ventilator or cardiopulmonary bypass produces oxidant damage with resultant functional depression that is not a result of cardiopulmonary bypass. These findings suggest that initiation of cardiopulmonary bypass in cyanotic immature subjects causes an unintended reoxygenation injury, which may increase vulnerability to subsequent ischemia during surgical repair.

Alkadienes↗
PubMed1995

Retrograde cardioplegia does not adequately perfuse the right ventricle.

UNLABELLED: Surgeons often rely primarily on retrograde cardioplegia for myocardial protection, because it provides adequate left ventricular perfusion even in the presence of coronary artery disease. Clinically, however, adequate right ventricular perfusion by retrograde delivery has not been demonstrated. Using intraoperative transesophageal echocardiography, we examined retrograde delivery of cardioplegic solutions by contrast echocardiography, which directly assesses myocardial perfusion. In 15 patients (seven having coronary bypass and eight having valve operations), 4 ml of sonicated Isovue medium was injected retrograde via a coronary sinus catheter. Myocardial perfusion was assessed quantitatively by visual inspection and back-ground-subtracted videodensitometric analysis. In five patients undergoing aortic valve replacement, right and left coronary ostial drainage was estimated during retrograde infusion. Before the aortic crossclamp was removed, myocardial oxygen extraction was calculated in all 15 patients by first delivering warm blood cardioplegic solution for 2 minutes in a retrograde fashion and then taking samples from the cardioplegia line and aortic root. This determined the oxygen extraction ratio across the myocardium at the end of retrograde delivery. Warm blood cardioplegic solution was next given antegrade, and 15 seconds later samples were taken from the cardioplegia line and a right ventricular (acute marginal) vein to determine the oxygen extraction ratio across the right ventricle. As assessed by contrast echocardiography, retrograde infusion resulted in almost four times more perfusion to the left ventricular free wall and septum than to the right ventricular free wall (74 +/- 2 versus 69 +/- 2 versus 20 +/- 2, p < 0.05). In those five patients with an aortotomy the right ostial drainage was less than 5 ml/min whereas left ostial drainage was estimated at 80 ml/min during retrograde administration. Oxygen extraction across the myocardium supplied by retrograde infusion was low after 2 minutes. Conversely, when antegrade cardioplegia was started, right ventricular oxygen extraction rose fourfold (42% +/- 5% versus 11% +/- 1%, p < 0.05), demonstrating that retrograde cardioplegia had not adequately perfused the right ventricular myocardium. CONCLUSIONS: 1. Retrograde cardioplegia provides poor right ventricular myocardial perfusion as assessed by contrast echocardiography and coronary ostial drainage. (2) This poor perfusion is inadequate to meet myocardial demands as demonstrated by the high right ventricular oxygen extraction after a prolonged retrograde infusion. (3) Therefore surgeons must not rely solely on retrograde cardioplegia for right ventricular myocardial protection. This concept is especially important if continuous warm blood cardioplegia is used, because myocardial requirements are then higher.

Blood↗
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

Conservation of human Y chromosome sequences among male great apes: implications for the evolution of Y chromosomes.

Nine newly described single-copy and low-copy-number genomic DNA sequences isolated from a flow-sorted human Y chromosome library were mapped to regions of the human Y chromosome and were hybridized to Southern blots of male and female great ape genomic DNAs (Gorilla gorilla, Pan troglodytes, Pongo pygmaeus). Eight of the nine sequences mapped to the euchromatic Y long arm (Yq) in humans, and the ninth mapped to the short arm or pericentromeric region. All nine of the newly identified sequences and two additional human Yq sequences hybridized to restriction fragments in male but not female genomic DNA from the great apes, indicating Y chromosome localization. Seven of these 11 human Yq sequences hybridized to similarly-sized restriction endonuclease fragments in all the great ape species analyzed. The five human sequences that mapped to the most distal subregion of Yq (deletion of which region is associated with spermatogenic failure in humans) were hybridized to Southern blots generated by pulsed-field gel electrophoresis. These sequences define a region of approximately 1 Mb on human Yq in which HpaII tiny fragment (HTF) islands appear to be absent. The conservation of these human Yq sequences on great ape Y chromosomes indicates a greater stability in this region of the Y than has been previously described for most anonymous human Y chromosomal sequences. The stability of these sequences on great ape Y chromosomes seems remarkable given that this region of the Y does not undergo meiotic recombination and the sequences do not appear to encode genes for which positive selection might occur.

Animals↗
PubMed1994

Warm blood cardioplegic induction: an underused modality.

Warm blood cardioplegic induction (WBCI) improves recovery of cardiogenic shock hearts by repaying their energy debt before cold ischemic arrest. This study tests the hypothesis that despite the absence of shock, many hearts are energy depleted and would benefit from WBCI. Twenty-five consecutive (nonshock) patients undergoing open heart operations received antegrade WBCI. Simultaneous samples were drawn from the aortic root and coronary sinus 15 seconds and 2 minutes after cardiac arrest. Samples were analyzed and compared to determine the oxygen consumption, oxygen extraction ratio, and glucose uptake across the left ventricular myocardium. There was a positive linear correlation between oxygen and glucose uptake (p < 0.001). By univariate analysis, severe multivessel disease and high Parsonnet (severity) score were predictors (p < 0.05) of increased metabolic uptake during warm induction. In addition, patients requiring urgent operations (unstable angina, left main disease, or congestive heart failure) and those with a history of hypertension (coronary artery bypass grafting) or left ventricular overload (valve patients) had higher consumption of oxygen and glucose (p < 0.05) compared with patients undergoing elective operations or those without a history of hypertension. In conclusion, warm cardioplegic induction in nonshocked hearts results in increased metabolic uptake indicating energy repayment and correlates with severity of underlying myocardial disease. The need for WBCI is especially great in patients with a history of hypertension or left ventricular overload and those requiring an urgent operation, where increased metabolic extraction was still present after 2 minutes. In addition, even for completely elective patients, WBCI may be useful if the patient has severe multivessel disease or a high Parsonnet score.

Adult↗