Norman Brachfeld

Myocardial uptake and fractional distribution of palmitate-1 C14 by the ischemic dog heart.

The left coronary artery of the dog heart was perfused in vivo with oxygenated whole blood containing physiologic concentrations of glucose and FFA labeled with palmitate-C14. Experiments were done at control and ischemic coronary flow rates. During ischemia, myocardial oxygen extraction rapidly became maximal and oxygen consumption fell 34 per cent. There was marked depression of myocardial contractility, elevation of filling pressure, and reversal of the normal pattern of lactate extraction. Extraction of palmitate label was inversely reiated to the coronary flow rate, increasing 97 per cent and maintaining consumption near control levels. The fractional distribution of extracted palmitate-1-C14 showed a significant shift with a decrease of label in tissue FFA and an increase in the triglyceride fraction. It is suggested that the histologic evidence of myocardial lipid accumulation noted, in association with hypoxia, is due to a stimulation of triglyceride synthesis from exogenous sources of FFA via the phosphatidic acid pathway. The increase in glycolysis associated with myocardial ischemia is the most likely source of the α-glycerophosphate needed for esterification.

Coronary Insufficiency: Relations Between Hemodynamic, Electrical, and Biochemical Parameters

Perfusion of the left coronary artery of open chest dogs at fixed control and ischemic flow rates demonstrated that ST alterations in the electrocardiogram were always associated with significant hemodynamic and metabolic changes. Decreased pressure time per minute, atrial hypertension, increased myocardial oxygen extraction, and the presence of excess lactate accompanied ischemia. In three dogs, hemodynamic changes, the presence of “excess lactate,” or both, preceded significant electrocardiographic changes. Whenever coronary flow was insufficient to meet myocardial oxygen demands, a series of metabolic shifts occurred. The most significant of these was inadequate aerobic energy production and stimulation of anaerobic glycolysis. This acceleration of anaerobic myocardial metabolism may be present without notably altering the surface electrocardiogram. The absence of ST shifts does not rule out the presence of concomitant and potentially severe myocardial ischemia.

Characterization of the ischemic process by regional metabolism.

The myocardial cell requires energy for contractile activity and for the work of internal maintenance. With the onset of ischemia mechanical performance is compromised. If the ischemia is severe and persistent, the energy necessary to maintain the internal millieu proves inadequate and cell death ensues. Ischemic heart disease is a regional phenomenon with normal and abnormal cell metabolism occurring side by side. The ischemic cell demonstrates hemodynamic, electrical and biochemical instability; its passage from a state of reversible to irreversible injury may persist for as long as 7 days and offers an opportunity to introduce interventions that may protect it and reduce ultimate infarct size. There is as yet no adequate objective means for predicting the mass of infarcted tissue. However, studies of regional metabolism, if properly conducted, may help define the adequacy of coronary vascular reserve and characterize the ischemic process. Current techniques utilize a myocardial pacing stress to induce an ischemic response. Although virtually every metabolic pathway is disrupted by severe ischemia, the assay of selected metabolities in arterial and coronary venous blood samples has provided information of diagnostic significance.

The Glucose-Insulin-Potassium (GIK) Regimen in the Treatment of Myocardial Ischemia

IN 1959 Selyel reported that myocardial resistance to cardiotoxic agents was reduced by intracellular hypokalemia and hypomagnesemia. Resistance was regained when this ionic imbalance was restored. Obstruction of a coronary artery inevitably causes a heterogeneous mixture of normal well-oxygenated, ischemically injured, and dead cells. This zone is biochemically and electrically unstable. Its progressively changing proportions are determined by many factors including the location of the site of vascular insufficiency, the magnitude of the collateral circulation, the condition of the cell prior to injury, the level of endogenous glycogen stores, and possibly by successful therapeutic intervention. Early ischemic changes are potentially reversible. Survival and recovery of normal function has been demonstrated despite total cessation of flow for periods of 20 to 60 min. The metabolic behavior of this zone of ischemia (the sick cell) most often determines the clinical course of the patient. Creatine phosphate (CP) and adenosine triphosphate (ATP) concentration fall rapidly after the onset of ischemia. There is an increase in intracellular adenosine di and monophosphate and in inorganic phosphate (Pi), the latter diffusing through the plasma membrane. Metabolic feedback controls permit an enhancement of anaerobic glycolysis supported by an increase in glucose transport and phosphorylation and in glycogenolysis. Glycogen depletion begins almost immediately. There is a shift of glycolytic intermediates to a

Perioperative Myocardial Infarction Associated with Coronary Artery Bypass Graft Surgery: Improved Sensitivity in the Diagnosis Within 6 Hours after Operation with 99mTc-Glucoheptonate Myocardial Imaging and Myocardial-Specific Isoenzymes

The present study was performed to evaluate scintigraphic imaging with technetium 99m-labeled glucoheptonate and serum enzyme levels of creatine phosphokinase isoenzyme (MB-CPK) in the early diagnosis of perioperative acute myocardial infarction associated with saphenous vein bypass graft operations. Myocardial imaging was done in 27 patients (50% of whom were considered high-risk) before operation and again 5 hours after operation. Four of these patients (15%) had both electrocardiographic and serum MB-CPK evidence of acute myocardial infarction, and all 4 had developed positive postoperative scintigrams. Four other patients had only elevated serum MB-CPK, and scintigrams became positive after operation in 3 of them. In addition, serum MB-CPK 6 hours after operation was 83 +/- 21 mIU/ml (mean +/- standard error of the mean) in patients with positive postoperative scans compared with 24 +/- 5 mIU/ml in those patients with negative postoperative scintigrams (p less than 0.001). Myocardial imaging with 99mTc-glucoheptonate in the perioperative period is rapid, safe, and atraumatic. Furthermore, our results suggest that it is a sensitive method for the early diagnosis of perioperative acute myocardial infarction, and, when imaging is combined with serum MB-CPK isoenzyme analysis, the reliability of the diagnosis of acute myocardial infarction is enhanced even further. Only 1 of the patients who showed perioperative myocardial damage had acute hemodynamic compromise or obvious impairment of recovery in the immediate postoperative period, and the 30-day mortality of the total group was 4% (1 of 27).

Metabolic evaluation of agents designed to protect the ischemic myocardium and to reduce infarct size

There is as yet no adequate animal mode for human myocardial ischemia. The commonly utilized technique of coronary arterial ligation in large animals may induce regional ischemia but introduces variables that make it difficult to compare studies in different laboratories. A model of global ischemia in an isolated perfused rat heart that offers a rapid, inexpensive means for producing graded, controlled, stable state and reproducible ischemia is described. The technique has been utilized with success to study the hemodynamic and metabolic effects of ischemia and to evaluate pharmacologic interventions designed to protect the ischemic myocardium. Propranolol has been shown to improve bioenergetics and reduce anaerobic glycolysis by a depression of the hemodynamic response of ischemic myocardium. Methylprednisolone appears to exert its primary effect by direct coronary vasodilation, increasing resting or control flow and providing an enhanced reserve when ischemia is imposed. Mannitol improves cardiac performance by reducing the increased myocardial cell water content induced by hypoxia or anoxia.

Surgical therapy of coronary arterial disease with special reference to myocardial revascularization

Abstract A review of the experimental and clinical data concerning myocardial revascularization by surgical means indicates that no procedure currently available will safely accomplish this purpose. Either there is no objective evidence of increased vascular supply greater than that resulting from ischemia, or the mortality has been prohibitive in those procedures in which coronary reserve has been improved. Although the majority of patients exhibit symptomatic improvement following all procedures, there is an equally significant clinical improvement following a sham operation. It is recommended that the frequency of angina pectoris be discontinued as a means of evaluating procedures designed to improve circulation to the myocardium. Use of this symptom should be replaced by objective methods which will determine coronary reserve.