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Gerald D Buckberg

Publications and source records attributed to Gerald D Buckberg.

44 records · Page 3Linked to original sources
PubMed2003

Blood cardioplegic protection in profoundly damaged hearts: role of Na+-H+ exchange inhibition during pretreatment or during controlled reperfusion supplementation.

BACKGROUND: Inhibition of the Na+/H+ exchanger before ischemia protects against ischemia-reperfusion injury, but use as pretreatment before blood cardioplegic protection or as a supplement to controlled blood cardioplegic reperfusion was not previously tested in jeopardized hearts. METHODS: Control studies tested the safety of glutamate-aspartate-enriched blood cardioplegic solution in 4 Yorkshire-Duroc pigs undergoing 30 minutes of aortic clamping without prior unprotected ischemia. Twenty-four pigs underwent 30 minutes of unprotected normothermic global ischemia to create a jeopardized heart. Six of these hearts received normal blood reperfusion, and the other 18 jeopardized hearts underwent 30 more minutes of aortic clamping with cardioplegic protection. In 12 of these, the Na+/H+ exchanger inhibitor cariporide was used as intravenous pretreatment (n = 6) or added to the cardioplegic reperfusate (n = 6). RESULTS: Complete functional, biochemical, and endothelial recovery occurred after 30 minutes of blood cardioplegic arrest without preceding unprotected ischemia. Thirty minutes of normothermic ischemia and normal blood reperfusion produced 33% mortality and severe left ventricular dysfunction in survivors (preload recruitable stroke work, 23% +/- 6% of baseline levels), with raised creatine kinase MB, conjugated dienes, endothelin-1, myeloperoxidase activity, and extensive myocardial edema. Blood cardioplegia was functionally protective, despite adding 30 more minutes of ischemia; there was no mortality, and left ventricular function improved (preload recruitable stroke work, 58% +/- 21%, p < 0.05 versus normal blood reperfusion), but adverse biochemical and endothelial variables did not change. In contrast, Na+/H+ exchanger inhibition as either pretreatment or added during cardioplegic reperfusion improved myocardial recovery (preload recruitable stroke work, 88% +/- 9% and 80% +/- 7%, respectively, p < 0.05 versus without cariporide) and comparably restored injury variables. CONCLUSIONS: Na+/H+ exchanger blockage as either pretreatment or during blood cardioplegic reperfusion comparably delays functional, biochemical, and endothelial injury in jeopardized hearts.

Animals↗
PubMed2003

A new role for cardioplegic buffering: should acidosis or calcium accumulation be counteracted to salvage jeopardized hearts?

OBJECTIVES: Thirty minutes of unprotected ischemia produced a jeopardized heart that was treated with a blood cardioplegic solution containing the natural erythrocyte and protein buffers. Cardioplegic pH was changed to 7.7 (buffered) or 7.2 (nonbuffered), and this was tested alone and after pretreatment with Na(+)-H(+) exchange blockade (cariporide) to define their protective effects. METHODS: Twenty-four Yorkshire-Duroc pigs (27-34.5 kg) underwent 30 minutes of normothermic global ischemia, followed by 30 minutes of aortic clamping during protection with buffered (n = 12) or nonbuffered (n = 12) glutamate-aspartate-enriched blood cardioplegic solution. Twelve hearts (6 buffered and 6 nonbuffered) were pretreated with intravenous cariporide (5 mg/kg) 15 minutes before ischemia. RESULTS: Severe and comparable left ventricle dysfunction followed buffered or nonbuffered cardioplegia: Preload recruitable stroke work recovered to 56% +/- 21% and 45% +/- 20% of baseline levels; creatine kinase MB, conjugated dienes, and myeloperoxidase activity markedly increased; moderate myocardial edema occurred; and endothelin-1 increased 2-fold more than baseline values. Cariporide pretreatment caused a similar return of preload recruitable stroke work to 86% +/- 9% and 90% +/- 6% after buffered or nonbuffered cardioplegia (P <.05 vs nonpretreated groups), allowed only minor creatine kinase MB and conjugated diene changes, and reduced endothelin-1 release 3-fold compared with hearts without sodium-hydrogen exchange blockage. CONCLUSIONS: The severe ischemia-reperfusion injury of 30 minutes of normothermic ischemia is not altered by an acidic or alkalotic pH cardioplegic solution. Correction of damage is achieved by adding Na(+)-H(+) exchange blocker therapy before treatment with buffered and nonbuffered solutions; thus, sodium-hydrogen exchange inhibition plays a more vital role in recovery than pH management.

Acidosis↗
PubMed2003

Conditioned blood reperfusion markedly enhances neurologic recovery after prolonged cerebral ischemia.

OBJECTIVES: To determine whether controlled reperfusion using conditioned leukodepleted blood can substantially limit cerebral reperfusion injury following prolonged ischemia. METHODS: Eighteen pigs (25-35 kg) underwent 90 minutes of hypothermic circulatory arrest (19 degrees C) to produce brain ischemia. At the start of rewarming, 10 pigs received uncontrolled reperfusion with unmodified (normal) blood. The other 8 pigs underwent 10 minutes of controlled reperfusion by selectively perfusing both common carotid arteries with blood passed through a CoBRA filter. This filter conditions the blood by removing white blood cells, platelets, and attenuating complement. Two other pigs underwent cooling and rewarming only (controls) without ischemia. Neurologic assessment was done using neurologic deficit scoring (0 = normal, 500 = brain death), and jugular venous samples were obtained for biochemical analysis postreperfusion. RESULTS: There were no statistical differences in hemodynamics between groups. At 6 hours postanesthesia, all animals receiving normal blood were substantially neurologically impaired. At 24 hours, they all had abnormal positioning and all but 1 were unable to sit or stand (neurologic score 124 +/- 19). In contrast, nonischemic controls and pigs receiving conditioned blood reperfusion showed only minor neurologic deficits at 6 hours, and at 24 hours all were considered normal (neurologic scores 0 and 6 +/- 5; P <.005 vs uncontrolled reperfusion). Compared with pigs receiving normal blood reperfusion, oxygen free radical formation (conjugated dienes 1.70 +/- 0.03 vs 1.60 +/- 0.02 Abs 240 nm; P <.05 vs uncontrolled reperfusion), and endothelin-1 release (2.12 +/- 0.09 vs 1.84 +/- 0.06 pg/mL; P <.05 vs uncontrolled reperfusion) were also significantly lower in animals receiving conditioned blood. CONCLUSIONS: Following prolonged cerebral ischemia, reperfusion injury is avoided by delivering conditioned blood, which is devoid of white cells, platelets, and membrane attack complex. These results suggest that this modality is clinically useful in situations where the brain is subjected to prolonged ischemia.

Animals↗
PubMed2003

Deep hypothermic circulatory arrest and global reperfusion injury: avoidance by making a pump prime reperfusate--a new concept.

OBJECTIVE: We sought to determine whether damage after deep hypothermic circulatory arrest can be diminished by changing pump prime components when reinstituting cardiopulmonary bypass. METHODS: Fifteen piglets (2-3 months old) were cooled to 19 degrees C by using the alpha-stat pH strategy. Five were cooled and rewarmed without ischemia (control animals), and the other 10 piglets underwent 90 minutes of deep hypothermic circulatory arrest. Of these, 5 were rewarmed and reperfused without altering the cardiopulmonary bypass circuit blood prime. In the other 5 animals, the bypass blood prime was modified (leukocyte depleted, hypocalcemic, hypermagnesemic, pH-stat, normoxic, mannitol, and an Na(+)/H(+) exchange inhibitor) during circulatory arrest before starting warm reperfusion. Oxidant injury was assessed on the basis of conjugated dienes, vascular changes on the basis of endothelin levels, myocardial function on the basis of cardiac output and dopamine need, lung injury on the basis of pulmonary vascular resistance and oxygenation, and cellular damage on the basis of release of creatine kinase and aspartate aminotransferase. Neurologic assessment (score 0, normal; score 500, brain death) was done 6 hours after discontinuing cardiopulmonary bypass. RESULTS: Compared with animals undergoing cardiopulmonary bypass without ischemia (control animals), deep hypothermic circulatory arrest without modification of the reperfusate produced an oxidant injury (conjugated dienes increased 0.78 vs 1.71 absorbance (Abs) 240 nmol/L per 0.5 mL, P <.001 vs control animals), depressed cardiac output (6.0 vs 4.0 L/min, P <.05 vs control subjects), prolonged dopamine need (P <.001 vs control subjects), elevated pulmonary vascular resistance (74% vs 197%, P <.05 vs control subjects), reduced oxygenation (P <.01 vs control subjects), increased neurologic injury (56 vs 244, P <.001 vs control subjects), and increased release of creatine kinase (2695 vs 6974 U/L, P <.05 vs control subjects), aspartate aminotransferase (144 vs 229 U/L), and endothelin (1.02 vs 2.56 pg/mL, P <.001 vs control subjects). Conversely, the oxidant injury was markedly limited (conjugated dienes of 0.85 +/- 0.09 Abs 240 nmol/L per 0.5 mL, P <.001 vs unmodified pump prime) with modification of cardiopulmonary bypass prime, resulting in increased cardiac output (5.1 +/- 0.8 L/min), minimal dopamine need (P <.001 vs unmodified pump prime), no increase in pulmonary vascular resistance (44% +/- 31%, P <.01 vs unmodified pump prime) or endothelin levels (0.64 +/- 0.15 pg/mL, P <.001 vs unmodified pump prime), complete recovery of oxygenation (P <.01 vs unmodified pump prime), reduced neurologic damage (144 +/- 33, P <.05 vs unmodified pump prime), and lower release of aspartate aminotransferase (124 +/- 23 U/L, P <.05 vs unmodified pump prime) and creatine kinase (3366 +/- 918, P <.05 vs unmodified pump prime). CONCLUSIONS: A global reperfusion injury after deep hypothermic circulatory arrest was identified and changed. The injury is mediated by oxygen-derived free radicals, resulting in organ and endothelial dysfunction. Modification of global organ and endothelial damage is achieved by modifying the blood prime in the cardiopulmonary bypass circuit to deliver a controlled global reperfusate when reinstituting bypass.

Animals↗
PubMed2002

Myocyte and endothelial effects of preconditioning the jeopardized heart by inhibiting Na/H exchange.

OBJECTIVES: The preconditioning effects of the adjunctive, cardiac-specific sodium-hydrogen ion exchange inhibitor cariporide (cariporide mesilate, HOE 642) were studied in hearts subjected to 30 minutes of normothermic ischemia and reperfusion to assess myocardial and endothelial changes. METHODS: Sixteen Yorkshire-Duroc pigs (27-34 kg) receiving cardiopulmonary bypass underwent either cardiopulmonary bypass alone (control, n = 4) or 30 minutes of normothermic ischemia, followed by 30 minutes of blood reperfusion (n = 12). Six hearts were treated with 5 mg/kg cariporide administered intravenously 15 minutes before ischemia. RESULTS: Cardiopulmonary bypass alone caused no changes. Conversely, 30 minutes of global normothermic ischemia caused 33% mortality and, in survivors, depression of left ventricular function to 22% +/- 6% of baseline preload recruitable stroke work and increased creatine kinase MB by 406% (88 +/- 13 U/L), conjugated dienes by 17% (161 +/- 0.2 AU/mL), and myeloperoxidase activity by 297% (0.036 +/- 0.005 U/g). Myocardial edema developed (3.5% water gain). Coronary sinus endothelin 1 increased by 111% (2.05 +/- 0.38 pg/mL), and nitric oxide production decreased by 10%. These adverse effects were limited by pretreatment with cariporide, which allowed complete survival and restored preload recruitable stroke work to 78% +/- 11%. Measurements of creatine kinase MB, conjugated dienes, myeloperoxidase, water, and endothelin 1 returned to baseline values, and nitric oxide production was accentuated 3-fold. CONCLUSIONS: These observations show that adjunctive pretreatment with cariporide delays myocardial and endothelial injury during ischemia and reperfusion, limits oxygen-derived radical injury, restores function, reduces edema, and preserves endothelin and nitric oxide balance at normal values. The myeloperoxidase changes show that less white blood cell adherence supports reduced reperfusion endothelial damage.

Animals↗
PubMed2002

Effects of leukocyte-depleted reoxygenation on endothelial and ventricular function: with observation of a short time period.

Postoperative myocardial global dysfunction causes mortality and morbidity in cyanotic congenital defects. This study investigates whether leukocyte depletion during coronary perfusion following reoxygenation can maintain endothelial and myocyte function, or less oxidant damage in a porcine neonatal model. After 30 minutes hypoxemia, 13 piglets underwent 60 minutes reoxygenation. The aorta was clamped and coronary reperfusion was either with normal blood (N=6), or leukocyte free blood by an inline filter (N=7). Cardiac function and endothelial response were assessed before and after cardiopulmonary bypass (CPB). Contractile recovery was improved by leukocyte depletion. Additionally, the antioxidant reserve capacity reserved more (534 36 versus 772 91; p<0.05) than reoxygenation without a leukocyte-depleting filter. Leukocyte depletion returned more extreme relaxation to acetylcholine (71.8 20.4% versus 41.2 9.8%; p<0.05), but did not change the endothelium-independent relaxation to sodium nitroprusside in either group. Activated leukocytes release oxygen free radicals that play a role in deterioration of the endothelial/myocardial function after reoxygenation and this deterioration in cyanotic heart diseases may be avoided by the use of the leukocyte-depleting filter.

Animals↗
PubMedDate not supplied

Myocardial protection: entering the new millennium.

Dual objectives at operation are technical success and absence of iatrogenic injury due to inadequate myocardial protection. We enter a new millennium, and the spectrum of surgical procedures used to correct abnormal structure is expanding. We need longer intervals of aortic clamping to make the correct diagnosis, and to implement a more natural correction (i.e., mitral valve repair, Ross procedure, aortic recontruction with stentless valves, homografts). Simultaneously, our patients have increased vulnerability to injury, so that growth is needed to advance our methods of protection, in the same way as we learn new operative techniques. This manuscript deals both with evolution of current methods and recognition of newer methods of protection, so that the dual relationship between protection and procedures will not separate.

Aortic Valve↗