Search PubMed⌕ Search

Biomedical subjects

G D Buckberg

Publications and source records attributed to G D Buckberg.

At least 109 records · Page 6Linked to original sources
PubMed1991

Studies of controlled reperfusion after ischemia. XX. Reperfusate composition: detrimental effects of initial asanguineous cardioplegic washout after acute coronary occlusion.

UNLABELLED: This study tests whether initial asanguineous washout of potentially toxic substances that accumulate during ischemia improves recovery produced by blood cardioplegic reperfusion and evaluates the role of plasma versus whole blood cardioplegia. METHODS: Twenty-four dogs underwent 2 hours of occlusion of the left anterior descending coronary artery and 20 minutes of blood cardioplegic reperfusion on total vented bypass. In 13 dogs, a 5-minute infusion of either a crystalloid (n = 7) or plasma (n = 6) cardioplegic solution (containing the same pH, calcium potassium, and osmolarity as blood cardioplegia) was given immediately before reoxygenation with blood cardioplegia. Regional oxygen uptake and coronary vascular resistance were measured during controlled reperfusion, and segmental shortening (ultrasonic crystals), tissue water content, and histochemical damage (triphenyltetrazolium chloride stain) were assessed 1 hour after bypass was discontinued. RESULTS: Asanguineous cardioplegic washout before reoxygenation with blood cardioplegic solution resulted in a progressive (+42%) increase in coronary vascular resistances (from 123 to 176 units, p less than 0.05) and low oxygen utilization during 20 minutes of blood cardioplegic reperfusion (29 ml/100 gm, p less than 0.05); coronary vascular resistance remained low throughout blood cardioplegic reperfusion without washout (from 109 to 98 units), and oxygen utilization was 54 ml/100 gm (p less than 0.05). Neither plasma nor crystalloid washout restored substantial regional systolic shortening (3% systolic shortening versus 73% systolic shortening with blood cardioplegia), and asanguineous washout caused more myocardial edema (81.1% +/- 80.9% versus 79.5% water content, p less than 0.05) and produced extensive transmural triphenyltetrazolium chloride damage (48% +/- 41% versus 8% nonstaining in area at risk, p less than 0.05) than initial blood cardioplegic reperfusion. CONCLUSION: Asanguineous cardioplegic washout before blood cardioplegic reperfusion limits oxygen utilization during subsequent controlled reperfusion, restricts early recovery of systolic shortening, allows more myocardial edema, and produces extensive histochemical damage, which may be avoided by initial reoxygenation with blood cardioplegia. The red blood cells appear more important than the plasma components of blood cardioplegia.

Adenosine Triphosphate↗
PubMed1991

Studies of controlled reperfusion after ischemia. XXI. Reperfusate composition: superiority of blood cardioplegia over crystalloid cardioplegia in limiting reperfusion damage--importance of endogenous oxygen free radical scavengers in red blood cells.

UNLABELLED: Postischemic damage is caused partially by oxygen free radical-mediated injury. This study will show that (1) crystalloid cardioplegia with room air oxygen is deleterious because it is devoid of free radical scavengers and (2) blood cardioplegia limits damage because it contains endogenous free radical scavengers in red blood cells. METHODS: Thirty-two dogs underwent 2 hours of ligation of the left anterior descending coronary artery followed by 20 minutes of regional blood cardioplegic reperfusion on bypass. Ten dogs received only the blood cardioplegic solution (containing its endogenous free radical scavengers); five received initial blood cardioplegia (5 minutes) with endogenous free radical scavengers (catalase and glutathione peroxidase) blocked by aminotriazole and N-ethylmaleimide, respectively; 12 received initial crystalloid cardioplegic solution oxygenated by room air (oxygen tension = 150 mm Hg); seven without and five with exogenous free radical scavengers (superoxide dismutase, catalase, coenzyme Q10); five received initial deoxygenated crystalloid cardioplegic solution (oxygen tension = 6 mm Hg); and five received deoxygenated crystalloid cardioplegic solution. RESULTS: Blood cardioplegia with endogenous free radical scavengers produced the best recovery of systolic shortening (69% systolic shortening) and resulted in the least histochemical damage (11% triphenyltetrazolium chloride nonstaining). The worst recovery and most damage occurred if blood cardioplegia was preceded by oxygenated crystalloid cardioplegia (3% systolic shortening, 48% triphenyltetrazolium chloride nonstaining; p less than 0.05 versus blood cardioplegia) or if free radical scavengers were blocked in the initial period of blood cardioplegia (3% systolic shortening, 41% triphenyltetrazolium chloride nonstaining; p less than 0.05 versus blood cardioplegia). Conversely, deoxygenation or supplementation of oxygenated crystalloid cardioplegic solution with exogenous free radical scavengers restored 60% systolic shortening (p less than 0.05 versus oxygenated crystalloid cardioplegia) and 54% systolic shortening (p less than 0.05 versus oxygenated crystalloid cardioplegia) and reduced damage to 34% and 21% (both p less than 0.05 versus oxygenated crystalloid cardioplegia). CONCLUSION: Blood cardioplegic solutions containing their own endogenous free radical scavengers are superior to crystalloid cardioplegic solutions, because they limit oxygen-mediated perfusion damage and restore contractile function. Initial crystalloid cardioplegic washout negates the salutary effect of blood cardioplegia. Exogenous free radical scavenger supplementation or deoxygenation of the cardioplegic reperfusate is necessary only if crystalloid cardioplegia is used.

Adenosine Triphosphate↗
PubMed1991

Studies of controlled reperfusion after ischemia. XXII. Reperfusate composition: effects of leukocyte depletion of blood and blood cardioplegic reperfusates after acute coronary occlusion.

OBJECTIVES: This study evaluates the role of leukocyte depletion during initial reoxygenation with normal blood and blood cardioplegic reperfusates in limiting reperfusion damage. METHODS: Twenty-eight dogs underwent 2 hours of ligation of the left anterior descending coronary artery. The initial reperfusate (37 degrees C) was delivered on total vented bypass to the left anterior descending artery by a calibrated pump via an internal mammary artery graft at 50 mm Hg for 20 minutes. Eight dogs received normal (normokalemic, nonenriched) blood reperfusion (leukocyte count 8000/mm3) and six were reperfused with leukocyte-depleted normal blood (leukocyte count less than 100/mm3). Of 14 dogs reperfused with substrate-enriched (hyperkalemic) blood cardioplegic solution, six received a cardioplegic solution with a leukocyte count less than 100/mm3. RESULTS: Leukocyte depletion of normal blood reduced reperfusion-induced arrhythmias from 63% to 17% (p less than 0.05). Coronary vascular resistance at initial reperfusion was low and remained low during substrate-enriched blood cardioplegic reperfusion with both normal and reduced leukocyte counts. In contrast, coronary vascular resistance rose 63% with normal blood reperfusion, and this increase was avoided by leukocyte depletion (2.6 versus 4.0 mm Hg x ml/min, p less than 0.05). Coronary vascular resistance after 20 minutes was, however, higher than that with blood cardioplegia with normal or decreased leukocyte counts. Negligible functional recovery followed reperfusion with normal blood and leukocyte-depleted blood (12% and 6% of control systolic shortening). In contrast, substantial segmental recovery followed blood cardioplegic reperfusion (73% systolic shortening, p less than 0.05) but was not improved by leukopheresis (81% systolic shortening). Leukocyte depletion of normal blood reperfusate reduced histochemical damage from 53% to 38% (p less than 0.05), but the least histochemical damage followed blood cardioplegic reperfusion with a normal or reduced leukocyte count (8% or 11%, p less than 0.05). CONCLUSIONS: These findings suggest an important role for leukocytes in reperfusion damage, but reperfusate leukocyte filtration alone is inferior to blood cardioplegic reperfusion. Leukocyte depletion of blood cardioplegic solutions seems unnecessary after only 2 hours of ischemia.

Animals↗
PubMed1991

Studies of controlled reperfusion after ischemia. XXIII. Deleterious effects of simulated thrombolysis preceding simulated coronary artery bypass grafting with controlled blood cardioplegic reperfusion.

This study tests whether simulated thrombolysis before controlled reperfusion (i.e., simulated coronary artery bypass) causes reperfusion injury that obviates the benefits of subsequent controlled reperfusion and results in unnecessary ventricular arrhythmias. Fifteen dogs underwent acute occlusion of the left anterior descending coronary artery. In 10 dogs we simulated thrombolysis after 1 hour of ischemia (delivering 10% to 15% of control flow at 5 ml/min), followed 1 hour later by either normal blood reperfusion at systemic pressure (to simulate percutaneous transluminal coronary angioplasty) in five dogs or regionally controlled blood cardioplegic reperfusion on bypass in five others to simulate coronary bypass. In five dogs ischemia was prolonged to 2 hours, and the initial reperfusate was blood cardioplegic solution on total vented bypass (to simulate primary coronary bypass). All hearts receiving simulated thrombolysis (100%) after 1 hour of ischemia had reperfusion-induced ventricular fibrillation. All hearts treated by simulated angioplasty recovered regional contractility (56% of control systolic shortening), whereas there was no (0%) recovery of spontaneous contractility after subsequent blood cardioplegic reperfusion, and only two (40%) dogs had contractile reserve capacity (6% +/- 49%). Conversely, surgically controlled blood cardioplegic reperfusion without preceding low-flow normal blood reperfusion after 2 hours of ischemia resulted in no ventricular arrhythmias (0%; p less than 0.05 versus simulated coronary artery bypass after simulated thrombolysis), 72% +/- 7% (p less than 0.05 versus simulated coronary artery bypass after simulated thrombolysis) recovery of regional contractility (ultrasonic crystals), and 114% +/- 11% (p less than 0.05 versus simulated coronary artery bypass after simulated thrombolysis) recovery of contractile reserve with calcium chloride stimulation. We conclude that controlled reperfusion (simulating coronary artery bypass) with blood cardioplegic solution produces immediate functional recovery and avoids the ventricular fibrillation that follows simulated thrombolysis despite the need for prolonged ischemic time. Preceding controlled reperfusion by normal blood reperfusion (simulated thrombolysis) shortens the ischemic time but nullifies immediate functional recovery possible by simulated coronary bypass and produces unnecessary arrhythmias.

Angioplasty, Balloon, Coronary↗
PubMed1991

[Antegrade and retrograde blood cardioplegia].

The article analyses the techniques of antegrade/retrograde blood cardioplegia which ensures even distribution of the solution in the heart so as to reduce the ischemic injury to the myocardium during compression of the aorta. The author describes methods of inducing cardioplegia by means of "warmed" blood for "reanimation" of the heart during cardioplegia and for the prevention of "reperfusion injuries" occurring immediately after the clamp is removed from the aorta. A method of rapid transatrial cannulation of the coronary sinus is described which provides for safe, rapid, and simple retrograde cardioplegia and helps to avoid isolation of the right heart. The theoretical basis of this operative technique is discussed as well as the specific methods for achieving the above mentioned purposes of using blood cardioplegia for resuscitation, avoidance, and prevention of ischemic and perfusion damages. Preliminary clinical experience in the use of antegrade/retrograde cardioplegia is generalized in this article. The results allowed us to introduce these methods of blood cardioplegia as an effective measure of myocardial protection during operations on adult patients and in some operations on children.

Cardiac Surgical Procedures↗
PubMed1990

Recent advances in myocardial protection using antegrade/retrograde blood cardioplegia.

This presentation details techniques of delivery of antegrade/retrograde blood cardioplegia to ensure its distribution to prevent ischemic damage during aortic clamping, and describes methods of using warm blood cardioplegia to "resuscitate" the heart when used to induce cardioplegia and "avoid reperfusion damage" when given just before aortic unclamping. A technique of rapid transatrial cannulation of the coronary sinus is described to permit safe, rapid, and simple use of retrograde cardioplegia and avoid right heart isolation. Theoretic objectives of these operative techniques are discussed, together with presentation of the specific methods of achieving the aforementioned goals of using blood cardioplegia for resuscitation, prevention, and avoidance of ischemic and reperfusion damage. The preliminary clinical experience with antegrade/retrograde cardioplegia is summarized, and these results have led to adoption of these techniques of blood cardioplegia as the preferred method of myocardial protection in all adult operations and in many pediatric cardiac procedures.

Aorta↗
PubMed1990

A new technique for delivering antegrade/retrograde blood cardioplegia without right heart isolation.

We report our updated experience with combined antegrade/retrograde cardioplegia using a self-inflating/deflating balloon cannula that allows rapid transatrial retrograde coronary sinus cannulation (10-15 s) without right heart isolation. This permits routine single venous cannulation and optimizes myocardial protection when combined with antegrade cardioplegia. Two hundred fifty-five consecutive patients underwent antegrade/retrograde cardioplegia. Initial antegrade blood cardioplegia caused immediate arrest (less than 1 min), and the cardioplegic dose was divided equally between antegrade and retrograde delivery. Included are 173 isolated CABG patients (39 with either extending infarction, cardiogenic shock, or ejection fraction less than 20%), and 37 coronary reoperations, 67 with aortic and/or mitral valve procedures, 3 with arrhythmia surgery, and 7 children (VSD, Rastelli, Konno, etc). Septal temperature in patients with LAD occlusion fell to 11.6 degrees C +/- 0.5 after retrograde vs only 16.1 degrees C +/- 3 after antegrade cardioplegia (p less than 0.05). Overall hospital mortality was 2.8% and no complications followed transatrial retrograde coronary sinus cannulation. Antegrade/retrograde cardioplegia allowed retrograde flushing of debris in redo coronary operations, produced immediate arrest with low cardioplegic volumes, improved cardioplegic distribution during IMA grafting, allowed aortic and mitral valve procedures to proceed uninterrupted, and ensured distribution in unforeseen aortic insufficiency. Antegrade/retrograde cardioplegia is now used routinely in all adult and in many pediatric operations because of its speed, safety, and simplicity.

Adolescent↗
PubMed1990

Studies of controlled reperfusion after ischemia. XVII. Reperfusion conditions: controlled reperfusion through an internal mammary artery graft--a new technique emphasizing fixed pressure versus fixed flow.

UNLABELLED: This study tests the usefulness of delivering a controlled reperfusate through an internal mammary graft after acute ischemia by applying a percutaneous technique of mammary artery cannulation and compares reperfusion at fixed pressure versus fixed flow. METHODS: Twenty-one dogs underwent 2 hours of ligation of the left anterior descending coronary artery followed by regional controlled revascularization on total vented bypass. A reperfusion catheter was introduced percutaneously from the brachial artery into the internal mammary artery. Five dogs received normal blood reperfusion at 50 mm Hg pressure, and eight dogs received a regional blood cardioplegic reperfusate at 50 mm Hg before reperfusion with normal blood. Eight additional dogs received regional cardioplegia at 30 ml/min for 20 minutes. Coronary vascular resistance, segmental shortening (ultrasonic crystals), tissue water content, and histochemical damage (triphenyltetrazolium chloride stain) were assessed. RESULTS: Reperfusion with normal blood increased coronary vascular resistance progressively to 62% above initial values (p less than 0.05) and failed to restore regional contractility (9% +/- 6% systolic shortening, p less than 0.05). In contrast, coronary resistance remained low throughout blood cardioplegic reperfusion at fixed pressure and the reperfused muscle recovered immediate contractility (73% systolic shortening, p less than 0.05). Controlled reperfusion at a fixed flow rate resulted in pressure that ranged from 30 to 80 mm Hg, slightly less recovery of systolic shortening (57%), and less return of contractile reserve (81% versus 114%, p less than 0.05). Regional blood cardioplegic reperfusion limited edema formation (79.5 versus 82% water content, p less than 0.05) and histochemical damage (11% versus 50% area of necrosis/area at risk, p less than 0.05). CONCLUSION: An internal mammary artery graft can be used effectively in the setting of acute ischemia if a controlled blood cardioplegic reperfusate is delivered through it to ensure limitation of histochemical damage, low reflow phenomenon, and restoration of immediate segmental contractility. Controlled-pressure reperfusion seems superior to fixed-flow reperfusion. A technique is described that may allow preoperative insertion of the reperfusion catheter in the internal mammary artery in the catheterization laboratory.

Adenosine Triphosphate↗
PubMed1990

Studies of controlled reperfusion after ischemia. XVIII. Reperfusion conditions: attenuation of the regional ischemic effect by temporary total vented bypass before controlled reperfusion.

This study tests the hypothesis that total vented bypass can attenuate the regional ischemic effect during a defined time interval before controlled blood cardioplegic reperfusion. Thirty-three dogs underwent 2 or 4 hours of occlusion of the left anterior descending coronary artery and then received a regional blood cardioplegic reperfusate on total vented bypass. Cardiopulmonary bypass and reperfusion were started after 2 hours of ischemia in eight dogs, and after 4 hours of ischemia in 25 others. Among the 25 dogs, seven had total vented bypass started after the first 2 hours of the 4 hours of regional ischemia. Segmental shortening (ultrasonic crystals), tissue water content (wet/dry weight), and histochemical damage (triphenyltetrazolium chloride stain) were assessed 2 hours after reperfusion. Dogs reperfused after 2 hours of ischemia recovered 73% +/- 8% of control systolic shortening and sustained only 11% triphenyltetrazolium chloride nonstaining. Dogs undergoing 4 hours of regional ischemia, but with total vented bypass 2 hours before reperfusion had improved recovery of systolic shortening (49% versus 31%, p less than 0.05), limited epicardial edema (79.6% versus 81.1% water content, p less than 0.05), and reduced histochemical damage (24% versus 39% triphenyltetrazolium chloride nonstaining, p less than 0.05). These findings imply that institution of total vented bypass during ischemia attenuates the infarct process, increases regional recovery of contractility, limits edema and restricts histochemical damage, and may be a useful adjunct to myocardial salvage when controlled reperfusion can be provided.

Adenosine Triphosphate↗
PubMed1990

Studies of myocardial protection in the immature heart. I. Enhanced tolerance of immature versus adult myocardium to global ischemia with reference to metabolic differences.

This study compares the metabolism and functional responses of adult and immature hearts to a standard ischemic insult. Ten adult dogs (25 to 27 kg) and 10 puppies (6 to 10 weeks old) underwent 45 minutes of aortic clamping on bypass. Preoperative and postoperative ventricular performance (Starling curves), biochemical factors, and water content were measured. Global ischemia in adults produced a 30% mortality rate (3/10) and low output syndrome in survivors (33% recovery of stroke work index). Conversely, all puppies survived and stroke work index returned to 85% of control, with less edema developing (0.4% versus 2% water gain, p less than 0.05). Puppies expended comparable glycogen stores but used more glutamate (15.4 versus 8.6 mumol/gm dry weight), produced more alanine (18.9 versus 6.4 mumol, p less than 0.05), succinate (19 versus 8.2 mumol, p less than 0.05), and malate (2.6 versus 0.15 mumol, p less than 0.05) during ischemia, and recovered better postischemic aerobic metabolism (410 versus 255 nmol tissue pyruvate, p less than 0.05). We conclude that tolerance of immature hearts to ischemia is related to amino acid utilization by transamination and increased substrate level phosphorylation, as occurring in diving mammals, suggesting retention of intrautero adaptive mechanisms.

Adenosine Triphosphate↗
PubMed1990

Studies of myocardial protection in the immature heart. II. Evidence for importance of amino acid metabolism in tolerance to ischemia.

This study tests the importance of amino acid transamination in determining the tolerance of immature hearts to ischemic damage. Amino acid transamination was inhibited metabolically by pretreatment with aminooxyacetic acid. The aminooxyacetic acid dose and duration were determined by incubating in vitro tissue homogenate and showing that an 8 mmol/L AOA dose for 5 minutes blocked 90% of alanine aminotransferase and aspartate aminotransferase activity. Control studies in nonischemic hearts showed that coronary perfusion with aminooxyacetic acid for 5 minutes did not impair myocardial performance. In contrast, pretreatment of immature puppies with aminooxyacetic acid severely impaired recovery after 45 minutes of normothermic global ischemia (30% versus 85% recovery in untreated hearts, p less than 0.05). Biochemical analyses of hearts undergoing ischemia showed aminooxyacetic acid to limit lactate production, impair glutamate utilization, prevent alanine production, and limit succinate accumulation (p less than 0.05). These data suggest that amino acid transamination is an important adaptive process in the immature heart that improves its resistance to ischemic damage.

Adenosine Triphosphate↗
PubMed1990

A new simplified method of optimizing cardioplegic delivery without right heart isolation. Antegrade/retrograde blood cardioplegia.

We report our initial experience with antegrade/retrograde cardioplegia using a self-inflating/deflating balloon cannula that allows rapid transatrial retrograde cannulation of the coronary sinus (10 to 15 seconds) without right heart isolation and permits routine single venous cannulation. We subjected 141 consecutive adult patients and nine children to antegrade/retrograde cardioplegia using rapid transatrial insertion of the Retroplegia cannula (Research Medical, Inc., Salt Lake City, Utah). Single venous cannulation was used in 116 patients having coronary artery bypass grafting or aortic valve replacement, or both. Initial antegrade blood cardioplegia caused immediate arrest (less than 1 minute) and the cardioplegic dose was divided equally between antegrade and retrograde delivery. Included are 95 patients having isolated bypass grafting (34 with extending infarction, cardiogenic shock, or ejection fraction less than 20%); 19 having coronary reoperations, 42 with aortic or mitral valve procedures, or both; and nine children having repair of congenital defects (e.g., repair of ventricular septal defect, Rastelli operation, Konno operation). Septal temperature in patients with occlusion of the left anterior descending coronary artery fell to 11.5 degrees +/- 0.5 degrees C after retrograde cardioplegia versus only 16 degrees +/- 3 degrees C after antegrade cardioplegia (p less than 0.05). The overall hospital mortality rate was 2% and no complications followed transatrial retrograde cannulation of the coronary sinus.

Adolescent↗
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

Antegrade/retrograde blood cardioplegia to ensure cardioplegic distribution: operative techniques and objectives.

This article details techniques of delivery of antegrade/retrograde blood cardioplegia to ensure its distribution to prevent ischemic damage during aortic clamping, and describes methods of using warm blood cardioplegia to "resuscitate" the heart when used to induce cardioplegia and "avoid reperfusion damage" when given just before aortic unclamping. A technique of rapid transatrial cannulation of the coronary sinus is described to permit safe, rapid, and simple use of retrograde cardioplegia and avoid right heart isolation. Theoretic objectives of these operative techniques are discussed, together with presentation of the specific methods of achieving the aforementioned goals of using blood cardioplegia for resuscitation, prevention, and avoidance of ischemic and reperfusion damage. The preliminary clinical experience with antegrade/retrograde cardioplegia is summarized, and these results have led to adoption of these techniques of blood cardioplegia as the preferred method of myocardial protection in all adult operations and in many pediatric cardiac procedures.

Blood↗
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↗