Biomedical subjects

B S Allen

Publications and source records attributed to B S Allen.

At least 55 records · Page 3Linked to original sources

PubMed1993

Superiority of controlled surgical reperfusion versus percutaneous transluminal coronary angioplasty in acute coronary occlusion.

Although percutaneous transluminal coronary angioplasty is successful in more than 90% of patients after acute coronary occlusion, overall mortality remains approximately 10% with higher subgroup mortality (i.e., occlusion of the left anterior descending coronary artery, multivessel disease, age older than 70 years, cardiogenic shock) and early recovery of regional wall motion is marginal. This multicenter report shows that controlled surgical reperfusion in patients with acute coronary occlusion reduces overall and subgroup mortality and restores substantial early contractility. In a survey from six institutions, 156 consecutive patients with acute coronary occlusion documented by angiography underwent surgical revascularization with controlled reperfusion using amino acid-enriched blood cardioplegic solution on total vented bypass. Ventricular wall motion was studied by echocardiography or multiple gated acquisition scan on postoperative days 5 to 7 and scored independently (0 = normal, 1 = mild hypokinesia, 2 = severe hypokinesia, 3 = akinesia, 4 = dyskinesia). Results are compared with results in 1203 patients with acute coronary occlusion treated by angioplasty in five reported medical series. Surgically treated patients were revascularized at longer ischemic intervals (6.3 versus 3.9 hours, p < 0.05) and had a greater incidence of left anterior descending occlusion (61% versus 43%, p < 0.05), multivessel disease (42% versus 22%, p < 0.05), and cardiogenic shock (41% versus 10%, p < 0.05), with 12 patients undergoing cardiopulmonary resuscitation en route to the operating room. Surgical results were superior in all categories, with overall mortality reduced from 8.7% after angioplasty to 3.9% after coronary bypass (p < 0.05). All surgical deaths occurred in patients with preoperative cardiogenic shock. Regional wall motion recovered significantly (score < 2) in 131 of 150 (87%) surgically treated patients with an average score of 0.9 +/- 0.8 (normal to mild hypokinesia) despite longer ischemic times.

Acute Disease↗

PubMed1992

Warm glutamate/aspartate-enriched blood cardioplegic solution for perioperative sudden death.

This report describes an initial experience applying warm glutamate/aspartate substrate-enriched blood cardioplegic solution to resuscitate hearts in 14 patients with witnessed perioperative arrest. Ten patients were in stable hemodynamic condition in the catheterization laboratory (n = 3) or intensive care unit when sudden irreversible fibrillation developed. It progressed to electromechanical arrest in six patients. In patients with preoperative or postoperative arrest, conventional cardiopulmonary resuscitation and defibrillation were unsuccessful and extracorporeal circulation was started 22 to 150 minutes after arrest. The left ventricle was vented, the aorta clamped, and warm (37 degrees C) aspartate/glutamate blood cardioplegic solution was given at a rate of 150 ml/min for 20 minutes. All bypass grafts were open with good flows in patients who had had coronary bypass, and coronary bypass was done in the three patients who had preoperative arrest. Eleven of 14 hearts resumed normal sinus rhythm after aortic unclamping, only two electrocardiographically proved infarctions occurred, and 13 patients had complete hemodynamic recovery with improved ejection fraction. Three patients died: one of progressive cardiogenic shock, another of mediastinitis, and the third of irreversible neurologic damage. Eleven patients were discharged from the hospital and are well after a follow-up period between 3 and 9 months. We conclude that witnessed perioperative arrest with intractable ventricular fibrillation should be treated aggressively by administering cardiopulmonary resuscitation during prompt transfer to the operating room for total vented bypass and delivery of warm substrate-enriched blood cardioplegic solution. This treatment may salvage hearts thought to be damaged irreversibly and may be a feasible approach to intractable witnessed cardiac arrest, provided cardiopulmonary resuscitation maintains satisfactory cerebral perfusion pressure.

Aged↗

PubMed1992

Topical cardiac hypothermia in patients with coronary disease. An unnecessary adjunct to cardioplegic protection and cause of pulmonary morbidity.

This retrospective analysis tests the hypothesis that topical cardiac hypothermia is an unnecessary adjunct to intraoperative myocardial protection and an avoidable cause of pulmonary morbidity in patients with coronary disease receiving blood cardioplegia. The hospital records of 150 nonrandomized consecutive patients undergoing elective and emergency isolated coronary revascularization were reviewed. All patients received multidose cold blood cardioplegia followed by warm blood cardioplegic reperfusion distributed through grafts. Fifty patients received iced slush, 50 received topical 4 degrees C saline, and no topical cooling was used in 50 others. Patients groups were comparable in number of grafts (3.7 versus 3.5 versus 3.5) and crossclamp time (61 versus 62 versus 61 minutes). More emergency operations were performed in the patients receiving no topical hypothermia (12/50 versus 8/50 versus 7/50). Postoperative x-ray films were reviewed by a radiologist who did not know of patient grouping. Postoperative results were comparable in hemodynamics, inotropic requirements (10/50 ice versus 8/50 saline versus 5/50 no cooling), myocardial infarction (1/50 versus 2/50 versus 2/50), and enzymes (aspartate aminotransferase myocardial band creatine kinase). No patient died. Ice topical hypothermia (versus no topical cooling) was associated with more left pleural effusions (25/50 versus 9/50; p less than 0.05), atelectasis (33/50 versus 18/50; p less than 0.05), elevated left hemidiaphragms (13/50 versus 0/50; p less than 0.05), and longer postoperative hospitalization (11.2 versus 8.5 days; p less than 0.05). Topical 4 degrees C saline reduced diaphragmatic elevation and pleural effusion (versus topical ice) but was associated with more atelectasis (34/50 versus 18/50; p less than 0.05) than no topical cooling. These data suggest that routine topical hypothermia is an unnecessary adjunct to blood cardioplegic protection in patients with coronary disease, since supplemental topical cooling does not improve postoperative hemodynamics or reduce inotropic requirements, enzyme release, or prevalence of postoperative myocardial infarction, and it increases pulmonary morbidity, which can be reduced by its avoidance.

Blood↗

PubMed1991

Single-copy flanking sequences in human histone gene clusters map to chromosomes 1 and 6.

Two single-copy sequences flanking two different human histone gene clusters were used as probes to map these clusters by in situ hybridization. pFF435B, a unique sequence subclone derived from a lambda genomic clone (lambda HHG55) containing H2A, H2B, H3, and H4 genes, mapped to chromosome 1q21 (chi 2 = 120.99, P less than 0.001). pST519E, a single-copy sequence derived from a lambda genomic clone (lambda HHG17) containing only H3 and H4 genes, mapped to chromosome 6p21 (chi 2 = 112.62, P less than 0.001). These findings agree with previous assignments of human histone genes to chromosomes 1 and 6 and demonstrate that the single-copy flanking sequences in different human histone gene clusters are unique for different chromosomes.

Chromosomes, Human, Pair 1↗

PubMed1989

Localization of the human type 5, tartrate-resistant acid phosphatase gene by in situ hybridization.

We report the localization of the gene for the human type 5, tartrate-resistant, iron-containing acid phosphatase isoenzyme (HGM designation ACP5) to chromosome 15 (15q22-q26) using the technique of in situ hybridization to metaphase chromosomes. We have localized this gene using peripheral blood chromosomes obtained from both a normal male and an individual carrying an unbalanced translocation involving chromosome 15 [45,XY,-15,-18,+der(18)-t(15;18)(q13;p11)]. In addition, we have demonstrated the utility of employing a standard fluorescent staining technique (distamycin/DAPI) to an emulsion-coated, Wright-stained, and destained chromosome preparation.

Acid Phosphatase↗

PubMed1989

Cardiogenic shock after acute coronary occlusion. Pathogenesis, early diagnosis, and treatment.

The early natural history of left anterior descending coronary artery (LAD) occlusion and the development of cardiogenic shock was studied in 35 open chest anesthetized dogs observed for 6 hours. Six control dogs underwent LAD isolation without occlusion, 13 underwent isolated LAD occlusion to simulate single vessel disease, and 14 underwent LAD occlusion and a 50% left circumflex coronary artery (LCA) stenosis to stimulate multi-vessel disease. Control dogs undergoing anesthesia showed no significant changes in hemodynamics after 6 hours. All dogs with single vessel disease survived and developed immediate and persistent dyskinesis of the anterior wall, a compensatory hypercontractility of remote muscle (131% of control)*, slight energy and substrate depletion and anaerobic metabolism (increased G6P)* despite maintenance of "normal" blood flow through the LCA. In contrast, early mortality was 57% in simulated multi-vessel disease as intractable ventricular fibrillation and/or cardiogenic shock caused the deaths of 7 of 13 dogs (57%)*. Remote muscle became progressively hypocontractile (61% of control)* and caused progressive reduction in stroke work index (less than or equal to 0.5 g x m/kg)*. Remote muscle showed moderate substrate and energy depletion (greater than or equal to 60% fall of ATP and CP, 37% fall of glutamate)* and more pronounced evidence of anaerobic metabolism (G6P rose 373%)* despite "normal" blood flow. These findings suggest that remote muscle is the principle determinant of mortality after an otherwise non-lethal cardiac event.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Studies on prolonged acute regional ischemia. V. Metabolic support of remote myocardium during left ventricular power failure.

This study tests the hypothesis that metabolic support of remote "nonischemic" myocardium during acute infarction will reverse the trend toward cardiogenic shock. Thirty-seven dogs underwent ligation of the left anterior descending coronary artery and 50% stenosis of the circumflex coronary artery. Irreversible ventricular fibrillation developed in 11 of them. The 26 survivors were observed for up to 6 hours; global and regional left ventricular function (cardiac index, stroke work index, ultrasonic crystals) and regional blood flow (radioactive microspheres) were measured. After 2 hours, eight dogs received an intravenous infusion of glutamate/aspartate, glucose-insulin-potassium, coenzyme Q10, and 2-mercapto-propionyl-glycine for 4 hours. Five dogs received the mannitol infusion to raise serum osmolarity 30 mOsm. Four additional dogs received the intravenous substrate infusions over 4 hours without undergoing ischemia. The substrate infusion for 4 hours caused no change in regional or global cardiac function in the four control dogs. Three of nine untreated dogs died of cardiogenic shock, and progressive left ventricular power failure occurred in the six others (40% decrease in cardiac index, 50% decrease in stroke work index, p less than 0.05) because of persistent dyskinesia in the left anterior descending region (-40% of systolic shortening, p less than 0.05) and hypocontractility in the circumflex region (48% of control systolic shortening, p less than 0.05), despite normal transmural blood flow in the posterior left ventricular wall (76 ml/100 gm/min). In contrast, in treated dogs, hypercontractility recovered in the circumflex segment (138% of systolic shortening) and stroke work index rose to control levels (91%) without a change in regional blood flow. Mannitol infusion did not improve hemodynamics or avoid the development of progressive left ventricular power failure. We conclude that cardiogenic shock after myocardial infarction is due, in large part, to impaired ability of "nonischemic" myocardium to maintain hypercontractility. This limitation can be prevented by metabolic support of viable muscle, and the data imply that intravenous substrate infusions may be helpful before definitive treatment (i.e., coronary artery bypass grafting) is undertaken.

Animals↗

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↗

PubMed1988

A long-range ordered structure in mitochondrial cristae revealed by a pathological structural modification.

An experimentally imposed 6-hr local ischemia in the anterior wall of the left ventricle in dog hearts leads to a structural modification of the mitochondria in the posterior wall with the cristae revealing a zig-zag pattern when viewed in cross sections. This pattern was found to reveal a change in the distribution of crista mass with an increase of mass at circumscribed regions in each crista membrane and a reduction of mass from the surrounding region in each crista membrane. The accumulation of mass contributed to the elevations that caused the zig-zag pattern. These elevations were distributed according to a tetragonal pattern with a periodicity of 850 A. The tetragonal pattern contributed by one crista membrane was translocated halfway along the diagonals of the tetrameric pattern of the other crista membrane within each crista. The change in mass distribution reveals differences in the strength of bonds that account for binding of the proteins to the cristae with strong bonds in the elevated regions, while enzymes less firmly bound are located in the surrounding region. The respiratory chain enzymes will then be located in the elevated regions and the soluble enzymes including the tricarboxylic acid cycle enzymes will be located in the surrounding region. The tissue in the posterior wall was functionally impaired and normal function was restored when substrate for oxidative phosphorylation was added to the blood perfusing the tissue. It is concluded that the functional impairment is a consequence of a partial breakdown of the structural organization of the tricarboxylic acid cycle enzymes. The discovery of a long-range structural order involving the entire cristae reveals that the enzymes of the multienzyme systems as well as those systems in the cristae are structurally highly organized and it excludes that the enzymes are randomly mixed and highly mobile.

Animals↗

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↗

PubMed1986

Biochemical studies: failure of tissue adenosine triphosphate levels to predict recovery of contractile function after controlled reperfusion.

This study tests the hypotheses that postischemic adenosine triphosphate levels are unreliable predictors of functional recovery, myocardial adenosine triphosphate concentration of less than 2 mumol/gm does not indicate irreversible damage, mitochondrial adenosine triphosphate generating capacity can be nearly normal despite low levels of tissue adenosine triphosphate and the failure to replenish adenosine triphosphate after ischemia is due to depletion of the adenosine nucleotide pool, which can be replenished partially by exogenous precursors (e.g., 5-amino-4-imidazolecarboxamide ribotide [AICAR]). Myocardial adenosine triphosphate was depleted to less than 2 mumol/gm by either global ischemia (37 degrees C aortic clamping) or regional ischemia (acute coronary occlusion). Reperfusion was either with normal blood or with substrate-enriched blood cardioplegic solution during total vented bypass. Tissue adenosine triphosphate content and mitochondrial adenosine triphosphate generating capacity were measured, and functional recovery was determined by right heart bypass function curves or regional segmental shortening (ultrasonic crystals). Hearts undergoing 15 minutes of global ischemia and normal blood reperfusion had impaired functional recovery (stroke work index = 58 +/- 5%; p less than 0.05 of control) despite adenosine triphosphate concentration greater than 2 mumol/gm. Transmural mitochondrial State 3 respiration averaged 83% of control values despite adenosine triphosphate levels of 1 mumol/gm in hearts undergoing 45 minutes of 37 degrees C global ischemia and 2 additional hours of aortic clamping with multidose glutamate-enriched blood cardioplegia. AICAR increased adenosine triphosphate to 2 mumol/gm (p less than 0.05), but functional recovery was nearly complete (stroke work index = 94 +/- 2% of control) and was comparable with and without AICAR. Hearts undergoing 4 hours of regional ischemia recovered 31 +/- 5% systolic shortening after controlled reperfusion despite tissue adenosine triphosphate less than 0.5 mmol/gm (15% of control), and they retained 63% adenosine triphosphate generating capacity. Postischemic adenosine triphosphate levels correlate poorly with functional recovery, and adenosine triphosphate levels less than 2 mumol/gm do not indicate irreversible ischemic injury. Low postischemic levels may be repleted partially by adenine nucleotide precursor supplementation (AICAR).(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗

PubMed1986

Histochemical studies: inability of triphenyltetrazolium chloride nonstaining to define tissue necrosis.

Triphenyltetrazolium chloride has been used to detect irreversibly damaged tissue after regional ischemia and reperfusion. We used this staining technique in our studies of myocardial ischemia and reperfusion and found that a transmural triphenyltetrazolium chloride nonstaining pattern is not an accurate predictor of myocardial necrosis: functional recovery occurs despite nonstaining. Mongrel dogs (n = 91) were anesthetized and made ischemic by ligation of the left anterior descending coronary artery. Regional myocardial function was assessed by means of ultrasonic crystals. Following 2, 4, or 6 hours of ischemia, the ligature was removed, and each heart was reperfused either in the working state or during total bypass with either normal blood or substrate-enriched blood cardioplegic solution of differing composition. The hearts were then removed and incubated in triphenyltetrazolium chloride at 37 degrees C for 20 to 40 minutes. The pattern of nonstaining in the area at risk varied from patchy subendocardial, to confluent subendocardial, to transmural and did not correlate with the recovery of regional contraction following ischemia. Mitochondrial ultrastructure was altered minimally in nonstained muscle, which regained contractile function after 6 hours of ischemia. Fifty-two of sixty-five hearts (80%) showing a transmural nonstaining pattern in the area of ultrasonic crystal placement recovered the capacity to shorten systolically immediately after controlled reperfusion during total vented bypass. These results show that the triphenyltetrazolium chloride staining method does not predict myocardial necrosis and that appropriate reperfusion following 2 to 6 hours of ischemia will result in recovery of myocardial shortening despite transmural nonstaining.

Animals↗