The effect of coronary bypass surgery on exercise-induced ventricular arrhythmias.

Ninety-one patients with angiographically proved coronary artery disease and stable angina were randomly assigned into surgical and medical therapy. Graded exercise tests were performed on entry into the study and repeated in 1 year. Ventricular arrhythmias during exercise and 8 minutes of recovery were studied. Arrhythmias were graded on a scale of 0 to 7 by their presumed severity. On entry, both groups were similar in the severity of coronary disease, exercise capacity, and frequency and severity of exercise-induced ventricular arrhythmias. At 1 year, the frequency and severity of arrhythmias remained unchanged in both groups, whereas the surgically treated patients showed a marked improvement in their exercise capacity (p less than 0.005). The medically treated patients had a slight deterioration in their work capacity which, however, did not achieve statistical significance (p = 0.08). Twelve patients died suddenly. In seven medically treated patients who died suddenly, the frequency and severity of ventricular arrythmias on exercise were not different from those of the rest of the medical patients. In the five surgically treated patients who died suddenly, one had multiform premature ventricular beats, a second developed ventricular fibrillation (2 years before dying suddenly), and a third had no arrhythmias during exercise. Two died before the 1 year evaluation. Successful coronary surgery improves exercise capacity without decreasing associated ventricular arrhythmias. Exercise-induced ventricular arrhythmias, with the exception of ventricular fibrillation, may not be closely associated with the risk of sudden death.     

Traumatic pulmonary artery--left atrial fistula: an unusual case of cyanosis in an adult.

Eighteen months after sustaining a stab wound to the left upper chest, a 59-year-old man presented with cyanosis and extertional dyspnea. Arterial desaturation due to a central 22 per cent right-to-left shunt was present. A selective pulmonary arteriogram demonstrated a fistula between the main pulmonary artery and the left atrium. At operation the fistula was closed. A laceration of the pulmonic valve and healed pericarditis were present. Marked symptomatic improvement followed the operation, but a murmur of pulmonic valvular regurgitation persisted. The fistula and laceration of the pulmonic valve were probably traumatic in origin.     

Ischemic myocardial injury during cardiopulmonary bypass surgery

ECG's and serum levels of SGOT, LDH, and CPK were examined during the immediate postoperative period in 126 patients who had cardiac surgery during cardiopulmonary bypass. None had coronary disease and valve replacement was performed in 97 patients. Miscellaneous procedures not involving the coronary arteries were performed in 29. In surviving patients, ECG signs of acute myocardial infarction appeared in 8 (7 per cent) and changes compatible with acute ischemic injury were seen in 38 (30 per cent). Elevation of SGOT exceeding 90 units occurred in 32 per cent of patients and LDH levels over 900 units occurred in 37 per cent. In patients with ECG evidence of postoperative infarction or ischemia, 70 per cent had abnormal SGOT levels and 70 per cent had abnormal LDH levels. In 40 patients with SGOT levels exceeding 90 units, 80 per cent had ECG evidence of acute infarction or ischemia. In 80 patients without ECG changes, only 10 per cent had SGOT levels exceeding 90 units. CPK levels correlated poorly with ECG evidence of ischemia or infarction. Patients who demonstrated ECG and serum enzyme evidence of ischemic injury or myocardial infarction had longer total perfusion times during surgery (P < 0.001) but no relationship to aortic cross clamp time was observed. ECG evidence of acute myocardial ischemia with elevation of serum enzymes is frequently observed following cardiopulmonary bypass surgery. Serial ECG's and measurements of postoperative serum enzymes provide useful information regarding myocardial injury and the effectiveness of bypass perfusion in protecting the myocardium during cardiopulmonary bypass sugery.     

Diagnostic value of Q-waves in inferior myocardial infarction

Forty-eight patients with proved, healed, inferior myocardial infarction were studied to determine the electrocardiographic characteristics of this syndrome, the correlation between electrocardiographic abnormalities and angiographic findings, and to determine the value of recording Lead III during inspiration to identify abnormal Q-waves.The diagnosis of inferior myocardial infarction (IMI) was established by the presence of two of the following three criteria: (1) past history of acute infarction, associated with typical acute electrocardiographic changes and compatible clinical data, (2) total occlusion or more than 80 per cent occlusion of the right coronary artery, and (3) contraction abnormalities of the inferior left ventricular wall.Fifteen per cent of patients with inferior myocardial infarction had diagnostic Q-waves in all the three limb Leads II, III, and aV_F, and 29 per cent of patients had no diagnostic Q-waves in any of the three limb leads. Relative frequency of diagnostic Q-waves in inferior myocardial infarction were found to be 70, 43, and 15 per cent in Leads III, aV_F, and II, respectively.One hundred per cent correlation was noted between left ventricular inferior wall asynergy and presence of diagnostic Q-waves in all the limb Leads II, III, and aV_F, but the correlation was low (54 per cent) when none of the limb Leads II, III, and aV_F revealed diagnostic Q-waves.Obtaining Lead III in deep inspiration to differentiate an abnormal Q-wave due to inferior myocardial infarction from a benign Q-wave was not found to be a reliable measure and could result in false-negative diagnosis of inferior myocardial infarction in a significant number of patients.     

Medical versus surgical treatment of unstable angina

Unstable angina is an important symptom of coronary artery disease. Two general clinical presentations may occur: (1) stable angina with a recent increase in severity or angina of recent onset, or (2) acute coronary insufficiency or angina at rest with chest pain resembling that of acute infarction. The risk of death or infarction is greater in patients who have recurrent chest pain and ST-T wave abnormalities despite hospital treatment. In patients without electrocardiographic or serum enzyme evidence of a completed infarct, coronary arteriography and bypass graft surgery can be performed with an acceptably low mortality rate. Surgical treatment provides better symptomatic relief than medical management in many patients, but the significant incidence of perioperative infarction makes it difficult to determine if surgery prevents infarction. Some studies indicate that surgery improves survival in subgroups, but data from large scale randomized studies will be needed to answer this question securely. Patients with disease of the left main coronary artery should probably have surgical treatment.Medical treatment will relieve symptoms in most patients with unstable angina and on a long-term basis may obviate the need for surgery. A preliminary period of intensive medical treatment before surgery may be advantageous since there is little evidence that survival rates are improved by treating unstable angina as an acute surgical emergency.     

Effects of coronary artery bypass grafting on resting and exercise hemodynamics in patients with stable angina pectoris: a prospective, randomized study.

In this prospective randomized study, resting and exercise hemodynamics were determined in the nonmedicated state before ("entry") and 1 year after coronary bypass surgery in 38 patients, and at entry and 1 year in 40 patients treated medically. The surgical group showed a significant decrease in mean pulmonary arterial wedge pressure during exercise (entry 23.5 +/- 6.1 [standard error of the mean] mm Hg, 1 year 18.9 +/- 1.0, P less than 0.02); an increase in cardiac index during exercise (entry 4.3 +/- 0.1 liter/min per m2, 1 year 4.6 +/- 0.1, P less than 0.05); an increase in resting mean arterial pressure (entry 94.5 +/- 2.2 mm Hg, 1 year 100.2 +/- 2.2, P less than 0.02); and an increase in resting heart rate (entry 68.5 +/- 1.9 beats/min, 1 year: 76.0 +/- 2.0, P less than 0.01). Maximal treadmill exercise performance also improved significantly in the surgical group of patients (entry 285 +/- 24 seconds, 1 year 382 +/- 24, P less than 0.002). There were no significant changes in these variables in the medically treated "control" group. The improvement in pulmonary arterial wedge pressure during exercise and in maximal treadmill exercise time in the surgical group as a whole was due to striking improvement in these variables in a subgroup of 16 surgical patients who had a more than 10 mm Hg increase in pulmonary arterial wedge pressure during exercise in their entry study. In this subgoup, considered to contain those patients with marked "ischemicdysfunction," pulmonary arterial wedge pressure during exercise fell from 31.4 +/- 1.5 mm Hg (entry) to 19.l +/- 1.8 (1 year) (P less than 0.0001) and treadmill time increased from 217 +/- 24 seconds (entry) to 357 +/- 37 (1 year) (P less than 0.001). Thus, hemodynamic evidence of ischemic left ventricular dysfunction during stress may identify those patients who will show objective improvement in ventricular performance after bypass graft surgery.     

Effect of coronary arterial bypass surgery on exercise-induced ventricular arrhythmias. Long-term follow-up of a prospective randomized study.

The effect of coronary arterial bypass surgery on exercise-induced ventricular arrhythmias and their relation to sudden death was examined in 102 patients with stable angina pectoris randomly assigned to medical and surgical therapy (54 and 48 patients, respectively). Symptom-limited treadmill tests were performed at entry and at 1 and 5 years. The surgical group demonstrated significant improvement in exercise performance at 1 year compared with the medical group, and at 5 years exercise-induced ischemia as evidenced by S-T depression and exertional angina remained substantially decreased in the surgical group with little change in the medical group. However, the frequency and severity of exercise-induced ventricular arrhythmias in each group remained unchanged at 1 and 5 years from those at entry. Similar results were obtained from an evaluation of ventricular arrhythmias in the electrocardiogram at rest. With the exception of exercise-induced ventricular tachycardia and fibrillation, no relation was found between ventricular arrhythmias and sudden death. Coronary bypass grafting does not decrease the frequency or severity of exercise-induced or resting ventricular arrhythmias. In patients with stable angina pectoris, with the exception of ventricular tachycardia and fibrillation, exercise-induced ventricular arrhythmias are poor predictors of sudden death. The data suggest that exercise-induced ventricular arrhythmias may not be related to ischemia but to other effects of exercise such as cardiac stimulation by catecholamines or other factors.     

Evidence that parathyroid hormone is not required for phosphate homeostasis in renal failure

Varying degrees of renal failure were produced by surgical reduction of renal mass in normal dogs and in thyroparathyroidectomized dogs (TPTX) in whom serum calcium levels were maintained in the normal range by the administration of vitamin D. Both groups of dogs maintained normal serum phosphate levels in spite of progressive decreases in glomerular filtration rates (GFR). Furthermore, both groups of dogs were able to increase the fractional excretion of phosphate as GFR decreased. Thus the same renal response to loss of GFR was maintained in the complete absence of parathyroid tissue. Finally, stable serum phosphate levels and increased fractional excretion of phosphate in response to a decrease in GFR were also demonstrated in acutely TPTX dogs who were not receiving vitamin D. These results indicate that phosphate homeostasis can be maintained in renal failure in the total absence of parathyroid hormone secretion.     

Unstable angina: comparison of medical and surgical management.

Medical versus surgical treatment of unstable angina was compared in a prospective nonrandomized study of 118 patients. Acute transient ST-T wave changes were present during chest pain in all patients. Acute infarction was excluded by serial electrocardiograms and enzyme studies. All patients admitted to the coronary care unit from 1970 to 1975 who fulfilled the entry criteria were included in the study. The starting point for data evaluation was 5 days after hospital admission. Characteristics at entry were similar in 66 medically treated patients and 52 patients who had coronary bypass vein graft surgery. During a mean follow-up period of 23 months in 66 medically treated patients with unstable angina the incidence rate of nonfatal myocardial infarction was 17% and the total mortality rate 21 percent compared with respective rates of 19% and 5.8% in 52 surgically treated patients. In the surgical group 8 patients (15%) had a perioperative infarction and only 2 (4%) had a late infarction; one patient (2%) died at operation. Symptomatic improvement was observed more frequently in the surgically treated group. Sixty percent of surgically treated patients were free of angina compared with 21% of medically treated patients. Eight medically treated patients (12%) required late surgical treatment for persistent severe angina despite optimal medical management.     

Removal of insulin by perfused rat liver: Effect of concentration

The kinetics of insulin removal by isolated rat liver were investigated by measuring the rate of disappearance of insulin from the perfusate during recycling perfusion and by comparing the extraction of insulin over a wide range of constant arterial hormone levels during nonrecycling perfusion. In the recycling studies, insulin was removed from the perfusing medium at a uniform rate between 5 and 45 min. The reaction velocity constant, or hepatic clearance, during this period of uniform disappearance averaged 1.8 ml/min and represented 34% of the volume flow through the liver. In the nonrecycling flow-through studies at constant arterial insulin concentration, an initial period of accelerated hepatic uptake of insulin was seen. This period lasted for 3 to 7 min, was seen at every level of arterial insulin concentration, and was followed by a period of constant hepatic insulin removal. The hepatic removal rate during the period of constant uptake increased in a linear fashion until arterial insulin concentration reached 500 μU/ml and attained a maximal value at concentrations over 800 μU/ml. These findings indicate that the time course of hepatic insulin uptake by the perfused rat liver consists of two phases—an initial rapid phase, possibly associated with insulin binding, followed by a sustained rate of insulin removal, which probably represents insulin utilization and degradation. The rate of hepatic insulin removal was found to be proportional to arterial insulin concentration over a range of 20 to 500 μU/ml. Above this concentration, hepatic removal processes became saturated, reaching a maximal value of 183 μU of insulin per gram of liver per minute.     

Medical versus surgical treatment of unstable angina

A prospective, nonrandomized data bank study of the effect of medical versus surgical management of patients with unstable angina included all patients with unstable angina seen at 1 hospital over an 8 year period. Patients were entered into the study after an initial 5 day period of medical treatment. Entry characteristics were similar in 104 surgical patients and 124 medical patients. The mean follow-up period was 52 months. The operative mortality rate was 2% (2 of 104). The incidence of operative infarction was 13% (13 of 104). Twentyseven medical patients (22%) had late surgery for progressive angina without operative mortality. Seven year survival (Mantel-Haenszel) was 65% for the medical group and 85% for the surgical group when analyzed by initial treatment (p = 0.012). Analysis by the crossover method where crossover medical patients are followed up only to the date of surgery yielded similar results (p = 0.008). Nonsurvivors were compared with survivors and had a higher incidence of the following entry characteristics: (1) age greater than 60 years; (2) diastolic blood pressure greater than 89 mm Hg; (3) ST-T changes in the resting electrocardiogram; (4) 3 vessel disease; (5) elevated left ventricular diastolic pressure (at rest); and (6) elevated left ventricular diastolic pressure (exercise). None had single vessel disease. The incidence of infarction (fatal and nonfatal) in 5 years was 17% in the medical group and 22% in the surgical group. In the latter group 13% had a perioperative infarct and 9% had a late infarct. Symptom relief was greater in the surgical group. At 5 years 62% had no angina and only 8% had severe angina compared with 37% and 24%, respectively, in the medical group. Thus surgical management of selected patients with unstable angina appears preferable to medical therapy in view of improved survival and greater symptom relief. Whereas the total incidence of infarction was not reduced this was, in part, related to a 13% incidence of perioperative infarction. Improved methods of myocardial protection have since reduced this incidence to 3.0% in our hospital.     

Effect of intravenous glucose infusion on plasma insulin removal rate

We have studied the effects of different intravenous glucose loads on the plasma insulin removal rates of constantly infused porcine insulin in dogs. Insulin removal was studied during infusions of exogenous insulin at rates of 20, 50, and 150 mU/min, and three different glucose loads were given during each of the three insulin infusions. Endogenous insulin secretion was suppressed by the constant administration of epinephrine and propranolol, and thus the resulting plasma insulin concentrations were entirely a function of entry and removal of the exogenously infused insulin. Consequently, at steady-state conditions, any change in rate of insulin removal would result in a reciprocal change in plasma insulin concentration. The steady-state plasma insulin concentrations were unchanged during the three different glucose infusions, and this was true at all three of the different insulin infusion rates. We conclude from the data that the rate of glucose administration and the subsequent blood glucose concentrations are without direct effect on plasma insulin removal.     

Cardiac arrest due to oral potassium administration

Cardiac arrest developed in two patients after the administration of oral potassium. Neither patient had renal insufficiency, but both had underlying heart disease. In one patient fatal ventricular fibrillation developed 4 days after he received an aortic valve replacement for aortic stenosis and while he was receiving oral potassium supplements. The serum potassium level before cardiac arrest was 8.1 meq. The second patient had angina and was given 40 meq of potassium orally 15 minutes after an exercise test which produced chest pain and S-T segment depression. One hour later, ventricular fibrillation developed. Resuscitation was successful. Both patients had electrocardiographic evidence of hyperkalemia. Oral administration of potassium may produce severe cardiac toxicity in patients with heart disease even when renal function is clinically normal.     

Hypercalcemia in acute uremia and following citric acid administration: differential effect on parathyroid gland microtubule content.

Hypercalcemia, which occurs 4 hr after bilateral nephrectomy in normal rats, is not seen 4 hr after either bilateral ureterotomy or sham surgery. These results indicate that it is loss of renal mass per se, not the uremic syndrome, which is responsible for the hypercalcemia. Citric acid levels also increase 4 hr after nephrectomy, and a degree of hypercalcemia and hypercitricemia comparable to that which follows nephrectomy can be produced by administration of citric acid to normal rats. In an attempt to evaluate the role of the parathyroid gland in the development of hypercalcemia in these two situations, the microtubule content of parathyroid gland chief cells was determined by ultrastructural sterologic techniques 4 hr after either bilateral nephrectomy or citric acid administration. The results of these measurements indicate that parathyroid gland chief cell microtubule content increases after citric acid administration but not following bilateral nephrectomy. The significance of these results is not clear. However, since a previous study has suggested a correlation between increased microtubule content and increased secretory status in the chief cell, one may speculate that increased microtubule content resulting from citric acid administration may also be associated with increased parathyroid hormone secretion. By this formulation, citric acid-induced hypercalcemia would be secondary to increased parathyroid hormone secretion, but the transient hypercalcemia that occurs after nephrectomy would take place in the absence of an increase in parathyroid hormone secretion. In this latter instance, it is possible that loss of the kidney, a major site of parathyroid hormone removal from plasma, leads to an increase in circulating parathyroid hormone level, and hypercalcemia, in the absence of an increase in hormone secretion rate.     

Evidence that hemodialysis does not improve the glucose tolerance of patients with chronic renal failure

Oral glucose tolerance tests were performed in 16 patients with chronic renal failure undergoing hemodialysis. In ten patients, studies were performed before and after one dialysis, while six patients were studied immediately prior to the start of chronic hemodialysis and just after the fifteenth dialysis. Hemodialysis did not lead to improvement in either the plasma glucose or growth hormone response to the oral glucose challenge. There was, however, a modest increase noted in the plasma insulin level 2 hr after the oral glucose challenge following dialysis. On the other hand, there was not any change in the overall relationship between the plasma glucose and insulin response to the oral glucose load as a result of dialysis. These results indicate that chronic hemodialysis as it is routinely conducted in the treatment of patients with chronic renal failure has, at best, a relatively modest effect on the plasma glucose, growth hormone, and insulin responses to an oral glucose challenge.