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Biomedical subjects

G D Buckberg

Publications and source records attributed to G D Buckberg.

At least 127 records · Page 7Linked to original sources
PubMed1989

Studies on prolonged acute regional ischemia. I. Evidence for preserved cellular viability after 6 hours of coronary occlusion.

Six hours of coronary occlusion has been thought to produce extensive and irreversible transmural damage and no possibility of salvage by reperfusion. This has been based on findings of adenosine triphosphate depletion and histochemical (triphenyltetrazolium chloride nonstaining) and ultrastructural changes (conventional preparatory techniques). This study tests the hypothesis that, in contrast to conventional wisdom, considerable structural and mitochondrial functional integrity remains in cardiac muscle subjected to 6 hours of regional ischemia. Twenty open-chest anesthetized dogs underwent isolation of the left anterior descending coronary artery and were observed for 6 hours. Eight of the 20 did not undergo ischemia and served as controls. Twelve underwent 6 hours of proximal ligation of the left anterior descending coronary artery (30% +/- 2% area at risk). Transmural biopsy specimens were analyzed. Coronary occlusion reduced regional blood flow (radioactive microspheres) to less than 10 ml/100 gm/min (p less than 0.05) and dyskinesia persisted in the area at risk for 6 hours. High-energy phosphates (adenosine triphosphate and creatine phosphate) declined to negligible levels and histochemical damage occurred (49% +/- 12% triphenyltetrazolium chloride non-staining). Mitochondrial ultrastructural changes (low protein denaturation embedding technique) were mild (the integrity of the inner and outer mitochondrial surface membranes and crystal membranes was maintained and myofibrillar degeneration did not occur). Mitochondrial oxidative phosphorylation rate remained at 63% of control levels, respiratory control index remained at 77%, and adenosine diphosphate/oxygen ratio was maintained at 96%. Mitochondrial Ca++ increased with lanthanum (from 26 to 46 nmol/mg protein, p less than 0.05), but irreversible calcium precipitation did not occur; calcium could be mobilized to normal levels (i.e., 13 nmol/mg protein) by ethylenediaminetetraacetic acid chelation. These data support our inference that necrosis does not occur after 6 hours of coronary occlusion and suggest that muscle salvage by reperfusion is possible after at least 6 hours of regional myocardial ischemia.

Adenosine Triphosphate↗
PubMed1989

Studies on prolonged acute regional ischemia. II. Implications of progression from dyskinesia to akinesia in the ischemic segment.

This study analyzed the pattern of regional wall motion in 58 dogs undergoing 4 to 6 hours of left anterior descending coronary artery occlusion. Regional wall motion was measured by ultrasonic crystals and ischemic muscle either remained dyskinetic (-40% of control systolic shortening, n = 26) or progressed toward akinesia (less than 20% of control systolic shortening or greater than 50% reduction in passive lengthening, n = 32). Ten dogs underwent unmodified blood reperfusion. Regional blood flow (radioactive microspheres), histochemical damage (triphenyltetrazolium chloride staining), and mitochondrial function were determined. Hearts showing persistent dyskinesia had more collateral flow (12 versus 2 ml/100 gm/min, p less than 0.05), less histochemical damage (26% versus 63% area at risk/area of nonstaining, p less than 0.05), and better retention of mitochondrial oxidative phosphorylation capacity (adenosine triphosphate, 622 versus 444 nmol/mg protein/min, p less than 0.05), and tended toward mitochondrial calcium accumulation (48 versus 64 nmol/mg protein). Unmodified blood reperfusion after 4 hours of ischemia produced prompt akinesia (-2% +/- 3% systolic shortening) and was associated with increased edema (82% water content), caused the low-reflow phenomenon (19% control subendocardial flow, 13 ml/100 gm/min), and increased histochemical damage (69% triphenyltetrazolium chloride nonstaining, p less than 0.05). These findings suggest that persistent dyskinesia during early ischemia (first 6 hours) may reflect a relatively optimistic sign, as regression to akinesia occurs in muscle with less collateral flow, more impaired mitochondrial function, worsened calcium homeostasis, and more severe histochemical and ultrastructural damage. These observations imply that careful evaluation of ischemic wall motion may provide a valuable insight into potential muscle salvage.

Adenosine Triphosphate↗
PubMed1989

Studies on prolonged acute regional ischemia. III. Early natural history of simulated single and multivessel disease with emphasis on remote myocardium.

The early natural history of left anterior descending coronary artery occlusion was studied in 35 open-chest anesthetized dogs observed for 6 hours. Six control dogs underwent isolation of the left anterior descending without occlusion, 13 underwent isolated occlusion of the artery to simulate single-vessel disease, and 14 underwent occlusion of the left anterior descending and 50% stenosis of the circumflex coronary artery to simulate multivessel disease. Regional systolic shortening was measured by ultrasonic crystals. Control dogs had a mild fall in cardiac output (27%) and rise in aortic pressure (15 mm Hg). Ischemia produced immediate dyskinesia (-60% of control systolic shortening), and passive lengthening persisted for 6 hours. All dogs with only occlusion of the left anterior descending artery survived (0% mortality). They were less prone to ventricular fibrillation (46% versus 79%, p less than 0.05), developed compensatory hypercontractility of remote muscle (131% of control systolic shortening, p less than 0.05), mild energy and substrate depletion, and anaerobic metabolism (increased glucose-6-phosphate, p less than 0.05) despite maintenance of "normal" blood flow. In contrast, the early mortality rate was 57% (p less than 0.05) when 50% circumflex stenosis coexisted. Intractable ventricular fibrillation and/or cardiogenic shock caused the deaths. Remote muscle became progressively hypocontractile (61% of control systolic shortening, p less than 0.05), with progressive reduction in stroke work index (less than 0.5 gm-m/kg, p less than 0.05). Remote muscle showed moderate substrate and energy depletion (greater than 60% fall of adenosine triphosphate and creatine phosphate, 37% fall of glutamate) and more pronounced evidence of anaerobic metabolism (glucose-6-phosphate rose greater than 400%, p less than 0.05) despite normal blood flow. Mitochondrial ultrastructure and function remained intact in all hearts. These findings suggest that remote muscle is the principal determinant of mortality after an otherwise nonlethal ischemic event. Functional deterioration despite normal blood flow to remote muscle suggests either autoregulatory failure or substrate depletion as a cause of hypocontractility. The structural and functional integrity of mitochondria in ischemic and remote myocardium implies that salvage is possible despite hemodynamic deterioration and intractable ventricular fibrillation.

Adenosine Triphosphate↗
PubMed1989

Studies on prolonged acute regional ischemia. IV. Aggressive surgical treatment for intractable ventricular fibrillation after acute myocardial infarction.

Of 21 dogs undergoing ligation of the left anterior descending coronary artery and 50% stenosis of the left circumflex coronary artery, 15 developed intractable ventricular fibrillation and underwent 1 added hour of femoro-femoral bypass. Three hearts were removed after 1 hour on bypass without myocardial reperfusion for biochemical and mitochondrial analysis. After the 1 hour, five underwent unmodified blood reperfusion on bypass; seven underwent 1 hour of aortic clamping on vented bypass to simulate coronary artery bypass grafting with multidose blood cardioplegic reperfusion. Regional systolic shortening was measured with ultrasonic crystals and cardiac output was measured by thermodilution techniques. All six hearts with no ventricular fibrillation or with reversible ventricular fibrillation and hearts that were not reperfused developed cardiogenic shock (40% decrease in stroke work index, p less than 0.05) because of persistent left ventricular dyskinesia (-40% of systolic shortening, p less than 0.05) and progressive circumflex hypocontractility (48% systolic shortening, p less than 0.05) and showed extensive (68%) triphenyltetrazolium chloride nonstaining. Two dogs died of left ventricular power failure (33% mortality rate). In contrast, 11 of 12 dogs that were reperfused could be weaned from bypass (8% mortality rate). The four dogs surviving after unmodified blood reperfusion (20% mortality rate) showed severe residual left ventricular dysfunction (39% of control stroke work index, p less than 0.05), had equivocal recovery of anterior contractility (10% +/- 7% of systolic shortening), had marginal recovery of contractility in the remote myocardium (60% +/- 11% of systolic shortening), and had extensive triphenyltetrazolium chloride nonstaining (58%). Conversely, all seven dogs with intractable ventricular fibrillation undergoing controlled reperfusion after 4 hours of ischemia recovered normal stroke work index (91%), regained 23% of systolic shortening in the region supplied by the left anterior descending coronary artery (p less than 0.05), 125% of systolic shortening in the circumflex region (p less than 0.05), and showed only 25% triphenyltetrazolium chloride nonstaining (p less than 0.05). These results suggest aggressive treatment of intractable ventricular fibrillation after acute myocardial infarction by providing reperfusion on bypass can salvage hearts thought previously to be damaged irreversibly.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Studies on prolonged acute regional ischemia. VI. Myocardial infarction with left ventricular power failure: a medical/surgical emergency requiring urgent revascularization with maximal protection of remote muscle.

Eighty consecutive patients receiving maximum inotropic and intraaortic balloon support underwent emergency coronary artery bypass grafting 3.4 +/- 1 days (mean +/- standard error) after infarction for severe left ventricular power failure (stroke work index less than 25 gm-m, left atrial pressure greater than 20 mm Hg). All underwent induction of cardioplegia with a 37 degrees C glutamate/aspartate blood cardioplegic solution, multidose cold (4 degrees C) replenishment, and warm reperfusate. Viable areas were grafted first to ensure cardioplegic distribution. Left ventricular power failure was reversed in 94% of patients; 75 of 80 patients had discontinuation of inotropic drugs and intraaortic balloon support. The early mortality rate (less than 30 days) was only 7% (3/45) with early operation (less than 18 hours) and rose to 31% (11/35, p less than 0.05) if operation was delayed more than 18 hours. Six of 14 early deaths were due to progression of preoperative organ failure despite reversal of shock. Eighteen of 66 early survivors died of end-stage heart failure (21/80), a 26% late mortality rate. Nonsurvivors (early and late) had a higher incidence of extending versus evolving infarction (33/64 versus 2/16, p less than 0.05), a longer delay from shock to operation (11/45 versus 24/35, p less than 0.05), more preoperative organ failure (9/9 versus 26/71, p less than 0.05), and a greater incidence of previous infarction (22/43 versus 13/37, p greater than 0.05). Thirty of 45 late survivors (67%) remain physically active. We conclude that left ventricular power failure should be considered a medical/surgical emergency that necessitates prompt angiography and can be reversed in selected patients. Postoperative mortality (early and late) is due principally to delay of operation leading to progression of preoperative organ failure or progression of underlying cardiac disease if infarction becomes established.

Emergencies↗
PubMed1989

Studies of retrograde cardioplegia. I. Capillary blood flow distribution to myocardium supplied by open and occluded arteries.

This study defines the nutritive (i.e., capillary) distribution of blood cardioplegic solutions delivered via retrograde and antegrade techniques to muscle supplied by open and occluded coronary arteries where myocardial segments are in jeopardy of inadequate cardioplegic protection. Open-chest anesthetized dogs were studied by mixing radioactive microspheres (15 +/- 5 microns) with a blood cardioplegic solution and administering cardioplegia either into the coronary sinus or into the proximal aorta with the left anterior descending coronary artery open or occluded (30% +/- 2% area at risk). Nutritive flow (i.e., percentage of delivered 15 microns microspheres trapped in myocardial capillaries) during retrograde infusions averaged 65% versus 87% with antegrade cardioplegia (p less than 0.05). Retrograde and antegrade cardioplegic nutritive flow to all left ventricular regions was comparable with the left anterior descending coronary artery open (65 versus 82 ml/100 gm/min, p greater than 0.05), and both methods provided preferential hyperperfusion of subendocardial muscle (endocardial/epicardial ratios 1.6 and 1.5, respectively). Nutritive flow to muscle supplied by the occluded left anterior descending coronary artery was preserved better by retrograde than antegrade cardioplegia (35 versus 5 ml/100 gm/min, p less than 0.05). Preferential subendocardial hyperperfusion was maintained during retrograde cardioplegia (52 ml/100 gm/min, endocardial/epicardial ratio 1.6), but flow was redistributed away from subendocardial muscle with antegrade cardioplegia (less than 2 ml/100 gm/min, endocardial/epicardial, 0.29, p less than 0.05). Left ventricular flow was reduced markedly during retrograde infusion with the left anterior descending coronary artery open or occluded (23 and 12 ml/100 gm/min), but septal cooling was superior to antegrade cardioplegia (15 degrees +/- 1 degree C versus 20% +/- 3%, p less than 0.05) despite near-normal antegrade septal flow (the left anterior descending coronary artery was ligated beyond the first septal branch). Right ventricular nutritive flow was only 7 ml/100 gm/min during retrograde coronary sinus perfusion and was maintained normally with antegrade cardioplegia.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Studies of retrograde cardioplegia. II. Advantages of antegrade/retrograde cardioplegia to optimize distribution in jeopardized myocardium.

This study tests the hypothesis that retrograde/antegrade cardioplegic delivery can overcome the limitations of poor cardioplegic distribution resulting from either technique alone and, potentially, may expand the safety of using internal mammary artery grafts in cardiac muscle in jeopardy of inadequate cardioplegic protection. Jeopardized myocardium was produced in 20 dogs by ligating the left anterior descending coronary artery for 15 minutes before starting cardiopulmonary bypass and by 1 hour of aortic clamping with multidose 6 degrees C cold blood cardioplegia. Five dogs received antegrade cardioplegia via the aortic root. Ten dogs received retrograde cardioplegia via the coronary sinus. Five additional dogs received retrograde/antegrade cardioplegia via both routes. The ligature on the left anterior descending coronary artery was removed after aortic unclamping, and regional myocardial temperature (thermistor probe), segmental shortening (ultrasonic crystals), and global left ventricular and right ventricular myocardial function were evaluated. Antegrade cardioplegia produced excellent right ventricular cooling (14 degrees C) and allowed complete right ventricular functional recovery. However, it failed to cool muscle supplied by the left anterior descending coronary artery (only 31 degrees versus 12 degrees C, p less than 0.05), postischemic global left ventricular function recovered only 38% (p less than 0.05), and segmental shortening in the region supplied by the left anterior descending coronary artery recovered only 22% (p less than 0.05). Retrograde cardioplegia produced homogeneous cooling (17 degrees C) and allowed near normal recovery of global and regional left ventricular function (99% and 86%), but right ventricular cooling was variable (19 degrees to 30 degrees C) and right ventricular function recovered inconstantly (range 64% to 100%, average 82%). The best myocardial protection occurred after retrograde/antegrade cardioplegia; myocardial cooling was homogeneous, left ventricular and right ventricular global function recovered completely (95% and 90%), and regional contractility in muscle supplied by the left anterior descending coronary artery returned to 84% of control. We conclude that retrograde/antegrade cardioplegia provides better myocardial protection than either technique alone, ensures good cardioplegic distribution to the left and right ventricles, and allows regional delivery of cardioplegic flow to segments supplied by occluded arteries.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Cardiac ischemia. Part II--Reperfusion and treatment.

An edited summary of an Interdepartmental Conference arranged by the Department of Medicine of the UCLA School of Medicine, Los Angeles. The Director of Conferences is William M. Pardridge, MD, Professor of Medicine.

Angioplasty, Balloon↗
PubMed1986

Reperfusion conditions: critical importance of total ventricular decompression during regional reperfusion.

This study tests the hypothesis that failure to minimize left ventricular oxygen demands by venting during reperfusion diminishes recovery after controlled blood cardioplegic reperfusion. Of 25 dogs undergoing 2 hours of left anterior descending coronary occlusion, nine were reperfused with normal blood without bypass and five were reperfused with normal blood during total vented bypass. Eleven other dogs were reperfused with aspartate-glutamate-enriched, diltiazem-supplemented blood cardioplegic solution for 20 minutes during cardiopulmonary bypass; the left ventricle was decompressed by venting in only five of them. Regional systolic shortening was measured by ultrasonic crystals and myocardial damage estimated from triphenyltetrazolium chloride staining. All segments developed systolic bulging during ischemia (-23% systolic shortening, p less than 0.05), with no segmental recovery after reperfusion with normal blood without bypass (-27% systolic shortening, p less than 0.05) and negligible recovery following reperfusion with normal blood during total vented bypass (6 +/- 2%, p less than 0.05). In contrast, there was immediate recovery of regional contractility (+ 53% systolic shortening, p less than 0.05) in bypassed hearts reperfused with aspartate-glutamate-enriched, diltiazem-supplemented blood cardioplegic solution when venting was used and triphenyltetrazolium chloride nonstaining fell from 43% to 12% (p less than 0.05). Conversely, there was no postischemic recovery (-8% systolic shortening, p less than 0.05) when the same blood cardioplegic reperfusate was given over a comparable time without venting; triphenyltetrazolium chloride damage increased to 25% (p less than 0.05). Minimizing O2 demands by left ventricular decompression with venting during blood cardioplegic reperfusion is essential to ensure immediate functional recovery and limit histochemical damage.

Animals↗
PubMed1986

Immediate functional recovery after six hours of regional ischemia by careful control of conditions of reperfusion and composition of reperfusate.

This study tests the hypothesis that irreversible muscle damage does not occur after as long as 6 hours of ischemia before reperfusion, immediate functional recovery is possible by controlling the conditions of reperfusion during total vented bypass and the composition of the reperfusate with substrate-enriched blood cardioplegic solution, and such control can be accomplished without thoracotomy. Of 43 dogs undergoing 2 to 6 hours of left anterior descending coronary occlusion, seven were studied by ultrastructural and mitochondrial analyses after 6 hours of regional coronary occlusion without reperfusion. Sixteen other dogs were reperfused with normal blood, with the heart in the beating state after 2 to 4 hours of ischemia, and 20 dogs received regional substrate-enriched blood cardioplegic reperfusion after 2 to 6 hours of ischemia for 20 minutes during total vented bypass accomplished through the femoral artery, femoral vein, and transaortic left ventricular venting. Six hours of ischemia without reperfusion caused minimal changes in mitochondrial structure and retained mitochondrial adenosine triphosphate production capacity at 64% of control values despite complete depletion of tissue adenosine triphosphate. Reperfusion with normal blood in the beating, working hearts caused extensive structural damage, reduced reflow, and failed to restore contractility in any instance (-27% systolic shortening, p less than 0.05). In contrast, regional cardioplegic reperfusion during total vented bypass at 2, 4, and 6 hours caused 52 +/- 3%, 41 +/- 7%, and 21 +/- 6% immediate recovery of regional contractile function. The seven hearts reperfused at 6 hours of ischemia had more segmental shortening (21% versus -27%, p less than 0.05), less edema (81% versus 83% water content, p less than 0.05), and more postischemic flow (57 versus 18 ml/100 gm/min in subendocardial muscle, p less than 0.05) than did 2-hour controls, and postischemic ultrastructure was not altered by reperfusion. Six hours of ischemia does not produce irreversible damage, and immediate recovery of contractile function is possible if the conditions of reperfusion are controlled with total vented bypass and a regional substrate-enriched blood cardioplegic solution is administered. Such control can be obtained by the peripheral cannulation technique.

Animals↗
PubMed1986

Early recovery of regional wall motion in patients following surgical revascularization after eight hours of acute coronary occlusion.

This study tests the hypothesis that failure of "successful" streptokinase with and without angioplasty to restore regional wall motion in patients with acute coronary occlusion is due to reperfusion injury that can be avoided in the surgical setting by control of the conditions of reperfusion and the composition of the reperfusate. Of 31 consecutive patients undergoing emergency coronary revascularization, 21 patients were reperfused medically with normal blood (streptokinase with or without angioplasty) following 4.5 +/- 0.4 hours of coronary occlusion in the coronary catheterization laboratory. Surgical reperfusion in 10 patients was with aspartate-glutamate-enriched blood cardioplegic solution during coronary artery bypass grafting after 8.5 +/- 0.5 hours (7.2 to 11.4 hours) of acute coronary occlusion. Hemodynamic instability was present in 5 of 10 surgical patients before operation and resulted from coronary occlusion, whereas 7 to 21 previously stable medical patients became unstable hemodynamically following revascularization with normal blood. Surgical patients evolved fewer electrocardiographically determined infarctions (7/10 versus 21/21, p less than 0.05), had fewer reperfusion ventricular arrhythmias (0/10 versus 9/21, p less than 0.05), had somewhat better global ejection fractions (47% versus 41%), and had shorter hospitalization times (8.3 versus 10.7 days, p less than 0.05); in addition, they all showed significant segmental contractility at discharge (10/10 versus 2/21, p less than 0.05), despite delay of revascularization up to 11 hours. No deaths occurred. These studies imply that acute coronary occlusion is treated best by control of the conditions of reperfusion and the composition of the reperfusate.

Aspartic Acid↗