Samuel C. Balderman

Perioperative Myocardial Infarction: A Diagnostic Dilemma

Patients undergoing coronary bypass grafting were studied for incidence of perioperative myocardial infarction (MI) using three modalities: serial electrocardiograms (ECG), serial creatine phosphokinase isoenzymes (MB-CPK), and serial technetium 99m-labeled pyrophosphate scans. A definite perioperative MI was diagnosed if the results were positive in two of the three variables studied. The perioperative infarction rate for the entire group was 8%. The operative mortality was 2.9%. Seven of 8 perioperative MIs were diagnosed by the use of scanning alone. The combination of isoenzyme and ECG analysis diagnosed 5 of 8 perioperative MIs. The MB-CPK and ECG studies were associated with a higher incidence of false-positive diagnoses than myocardial scanning. Patients with perioperative MI had a benign clinical course. Justification for performing three routine 99mTc-pyrophosphate scans on all patients undergoing aortocoronary bypass operation is still to be determined.

Preparation of venous allografts. A comparison of techniques.

In order to evaluate alternate techniques of preparing veins for use as homografts, 102 femoral veins were harvested from adult mongrel dogs. The veins were treated in four different ways, then transplanted into recipient animals bypassing their ligated femoral arteries. Group I--24 veins (6 cm each) were harvested and immediately transplanted. Group II--24 veins were stored in 15% dimethyl sulfoxide (DMSO) solution at -120 C for 21 days prior to transplantation. Group III--26 veins were stored for 21 days in plasminate solution at -60 C prior to use as allografts. Group IV--28 veins were stored in 0.5% gluteraldehyde solution for 21 days prior to implantation. Animals were randomly sacrificed at 1-month, 2-month, 6-month, and 12-month intervals. Patency of the transplant was determined weekly by ultrasound. Specimens were sent for light and scanning electron microscopy at the time of harvest, prior to implantation, and at sacrifice. Endothelial damage was graded on a scale of 0-16. Veins in Group II had a significantly higher patency rate (68% at 1 year) than Group III (35%) and Group IV (11%) (p less than 0.05). The intimal layer of all patent vessels was replaced by an organized mural thrombus. Partial endothelialization of the luminal surface was most prevalent in Group II. Intimal damage related to storage technique was significant in Group III (p less than 0.01). At sacrifice, severe endothelial damage was present in all groups (p less than 0.01). In conclusion, veins stored in 15% dimethylsulphoxide (DMSO) solution at -120 C have immunologic and physical characteristics that yield patency rates acceptable for clinical use when autogenous tissue is not available.

The Optimal Temperature for Preservation of the Myocardium during Global Ischemia

To determine the myocardial temperature that provides maximal preservation of the heart during global ischemic arrest, five groups of dogs were studied (6 per group). In all animals, the aorta was cross-clamped for 120 minutes. Serial biopsies were done for determination of adenosine triphosphate and creatine phosphate, and study by electron microscopy. Starling curves were derived prior to cardiopulmonary bypass and 60 minutes after bypass. Mitochondrial changes were graded on a scale of 0 to 4. In the control group (Group 1), the aorta was clamped when the rectal temperature reached 25 degrees C (myocardial temperature, 18 degrees to 22 degrees C). In Groups 2, 3, 4, and 5, myocardial temperature was maintained at 6 degrees C, 10 degrees C, 14 degrees C, and 18 degrees C (all +/- 2 degrees C), respectively, by the use of systemic and topical hypothermia and repeated injections of cold cardioplegic solution into the aortic root. All groups showed a depression of left ventricular stroke work index, particularly Group 1 (no survivors), Group 2, and Group 3. The high-energy phosphate stores were well preserved in all groups except Group 1. The mitochondrial ultrastructure showed significant changes in all groups, especially Groups 1 and 5. These data indicate that satisfactory preservation of mitochondrial ultrastructure and high-energy phosphates was achieved at myocardial temperatures lower than 18 degrees C. Extreme hypothermia (Groups 2 and 3) was associated with significant reduction in ventricular function under the experimental conditions employed.

Cardioplegic arrest of the myocardium with calcium blocking agents

This study was designed to compare the effects of the calcium slow channel blocking agents verapamil (0.15 mg/kg), diltiazem (0.15 mg/kg), and nifedipine (50 micrograms/kg) on the myocardium after global ischemia and reperfusion in the in situ canine model. Animals were subjected to 120-min normothermic global ischemia, followed by 45-min reperfusion. Cardioplegic arrest of the myocardium was achieved by administering one of the three calcium antagonists in a multidose fashion. Superior preservation (p less than 0.01) of left ventricular (LV) systolic function was achieved in group I (verapamil cardioplegia). dP/dt, at an intraventricular balloon volume of 25 cc, was 83% of control after reperfusion in group I. Group II (diltiazem) and group III (nifedipine) achieved only 55 and 63% of their preischemic dP/dt values. LV chamber stiffness was increased in hearts protected with nifedipine. The exponential constant m was increased from 0.04 +/- 0.01 to 0.08 +/- 0.01. Coronary blood flow after reperfusion increased from 120 to 184 cc/100 gr/min in group I (p less than 0.01). The hyperemic response in group III was negligible. The O2 consumption of the reperfused myocardium was not significantly altered in any of the treatment groups. Lactate metabolism during ischemia and after reperfusion was similar in all groups. ATP values were markedly reduced in all groups (p less than 0.05). Immediately after ischemia, ATP was 50, 28, and 44% of control in group I, II, and III, respectively. The excellent preservation of systolic function and a physiologic hyperemic response by verapamil could not be correlated with improved preservation of high-energy compounds or with significant changes in myocardial O2 consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Opposite effects of metallothionein I and spermine on mitochondrial function.

Previously, we reported that the stress-induced protein metallothionein I (MT) modulated the oxygen consumption (VO2) of isolated rat liver mitochondria [Life Sci. 55 221-226, 1994]. We now present confirmation of this finding, and the additional observations that in rat liver mitochondria, MT caused swelling and depolarization. These actions of MT were inhibited by the aliphatic polyamine, spermine. Our findings suggest that mitochondrial function could be influenced by the balance between MT and spermine.

Perioperative Protection of the Myocardium in Patients with Impaired Ventricular Function

Seventeen patients with poor ventricular function and severe coronary artery obstruction were operated on employing hypothermic potassium cardioplegic solution for myocardial preservation. Preoperatively and postoperatively, serial hemodynamics, electrocardiograms (ECG), MB-CPK studies, and technetium pyrophosphate scans were obtained for all patients. All ECGs and scans were negative for perioperative infarction. Peak MB-CPK levels were 40 +/- 25 units per liter. Two patients had MB-CPK levels suggestive of perioperative myocardial infarction. The preoperative cardiac index was 2.8 +/- 0.8 L/min/m2 and remained the same in the perioperative period. Stroke work index and total peripheral resistance were within normal range and remained constant throughout the period of study. Three patients required epinephrine (0.5 micrograms per minute) during the first 6 hours postoperatively, and in 2 patients an intraaortic balloon was inserted prophylactically and removed on the second postoperative day. Good myocardial preservation can be achieved in patients with severe coronary artery obstruction and preexisting left ventricular dysfunction using hypothermic potassium cardioplegic solution.

A Comparison of the Safety, Efficacy, and Distribution of Ceforanide and Cephalothin in Coronary Artery Bypass Graft Surgery

Antibiotic prophylaxis in open-heart operations is a widely accepted practice. Introduction of new antibiotics with differences in tissue distribution, spectrum of activity and therapeutic index prompts their evaluation as possible effective prophylactic agents. We compared the distribution, clinical efficacy, and safety of ceforanide with cephalothin as a prophylactic agent in coronary artery bypass graft (CABG) procedures. The results indicated that the intravenous administration of ceforanide at the dose of 1 gm every 12 hours for 2.5 days was equivalent to cephalothin 1 gm every 6 hours for 2.5 days. Serum, muscle, and bone concentrations of ceforanide were significantly greater than those of cephalothin. These concentrations consistently exceeded the minimal inhibitory concentration for Staphylococcus aureus, the major pathogen implicated in wound infections. No toxicty was observed with either antibiotic. Ceforanide merits consideration as a prophylactic antibiotic in CABG operations.

Parasternal Intrapleural Colon Interposition: An Alternative Pathway for the Colon Graft

A new pathway for the placement of the interposed colon in esophagocolonoplasty is described. In a patient with a peptic stricture and a history of previous coronary artery bypass operation and multiple thoracotomies, the interposed colon was placed in the parasternal right intrapleural space successfully. This avoided a thoracotomy as well as the areas of adhesion. Technical details are described.

Metallothionein metal composition is a determinant of its induction of the mitochondrial permeability transition

Metallothionein is rapidly induced by a broad range of stress mediators, such as interleukin 1, interleukin 6, interferon gamma, steroids, and catecholamines [1]. Mitochondria play a significant role in stress through the production of ATP, oxygen free radicals [2], maintenance of intracellular calcium homeostasis [3], and the initiation of apoptosis [4]. Our initial finding was that apometallothionein was capable of transferring electrons to cytochrome c [5]. Since cytochrome c is a component of the mitochondrial respiratory chain we hypothesized that metallothionein would modulate mitochondrial function. As these experiments progressed we were encouraged by the finding of Sakurai et al that the organelle with the highest amount of metallothionein was the mitochondrion [6].