Fine structure of cells and their histologic organization within internodal pathways of the heart: clinical and electrocardiographic implications.

The fine structure of the normal internodal pathways was studied in 1 human and 2 canine hearts and correlated with histologic observations on more than 100 human and 10 canine hearts. From the electron microscopic studies six different kinds of myocardial cells were classified from two locations: the Eustachian ridge (posterior internodal pathway) and the Bachmann bundle (anterior internodal pathway). Five of the six kinds of cells (working myocardial cells, Purkinje-like cells, either broad or slender transitional cells and P cells, all previously described) were present in both locations. A sixth cell, pleomorphic and dark in appearance, with a special intertwined relation to P cells, is newly designated as an ameboid cell. It was found solely in the Eustachian ridge. In the same area a rare direct contact between a nerve and a myocardial cell was observed. The importance of these different kinds of cells, their respective cell connections, and their topographic locations inside the internodal pathways are discussed relative to certain functions such as rapid conduction and subsidiary pacemaking. The possible influence of these factors on clinical electrocardiographic changes is considered.     

Reflex heart block: Baroreflex, chemoreflex and bronchopulmonary reflex causes

Reflex heart block was studied in 20 dogs anesthetized with sodium pentobarbital and in 5 trained unanesthetized dogs. Three different vagal reflexes were produced: the Marey response during hypertension caused by administering methoxamine, a cardiogenic hypertensive chemoreflex activated by injection of serotonin into the left atrium and the Hering-Breuer reflex observed during normal respiration of unanesthetized dogs. In every dog during any of the three reflexes heart block was consistently observed after the normal slowing response of the sinus node had been selectively eliminated by the direct perfusion of 10 μg of atropine into the sinus node artery. This was a uniform response despite its being variously produced by a pressor reflex, a chemoreflex or an extracardiac bron-chopulmonary reflex. Transient heart block is therefore to be anticipated during reflexes with vagal efferent components if for any reason the sinus node is incapable of slowing suitably. The possible clinical relevance of these experimental observations is discussed.     

Anatomic and physiologic considerations of a cardiogenic hypertensive chemoreflex.

Within both human and canine hearts there is a mass of chemoreceptor tissue lying just between the origins of the aorta and pulmonary artery and receiving its blood supply from the proximal portion of the left coronary artery. In the dog this is considered to be the site of origin for a powerful hypertensive reflex stimulated by serotonin. There is brief generalized arterial vasoconstriction, except for the coronary and pulmonary arteries. The afferent limb of this cardiogenic hypertensive Chemoreflex courses in thoracic branches of the vagus. Autonomic efferent responses are both vagal arid, sympathetic events. These include simultaneous positive and negative inotropic effects on the atria, a positive inotropic effect on both ventricles, positive and negative chronotropic actions and similarly mixed dromotropic effects. Methods for separately identifying and quantifying these responses are discussed and illustrated. Vagotomy eliminates the reflex, as does the administration of cyproheptadine (but not methysergide). Among possible human counterparts for this cardiogenic hypertensive Chemoreflex are the pressor responses associated with angina pectoris, with very early acute myocardial infarction and after certain forms of cardiac surgery such as saphenous vein bypass grafting.     

Primary and secondary cardioneuropathies and their functional significance

For most functions of the heart its nerves are as important as its coronary arteries, but this is particularly true concerning cardiac rhythm, conduction and repolarization. It is thus paradoxical that postmortem correlative studies of sudden death virtually always include careful scrutiny of the coronary arteries but only rarely of the cardiac nerves or ganglia. In this review, abnormalities of the cardiac nerves and ganglia, collectively termed cardioneuropathies, are examined from the dual standpoint of their structural appearance and functional significance. Some cardioneuropathies are found in the absence of any other significant structural abnormality detectable in the heart and these are designated as primary cardioneuropathies. A viral etiology or some heritable disorder must rank high among possible causes. Secondary cardioneuropathies are those observed in association with almost every disease that can affect the heart; examples include myocardial infarction, infections, amyloidosis and cancer, but there are many others. Because abnormalities of the heart's nerves and ganglia not only have their own unstabilizing influence on cardiac electrical activity but can also profoundly alter a patient's responses to pharmacologic treatment, it is hoped that future clinicopathologic examinations will more often include their careful study and thereby add to our meager knowledge about these important structures.     

Chance and sudden death

An aura of mystery has always surrounded the subject of sudden unexpected death. Part of the explanation is an absence of a single or usual explanation, although electrical instability of the heart does serve as a unifying concept for the final common pathway. In this review, emphasis is placed on the random aggregation of a wide variety of contributing factors in the pathogenesis of sudden death. Such factors include coronary disease, platelet aggregation, neural control of the heart, apoplexy of the heart, normal and abnormal variations in the structure of the atrioventricular junction, lessons from certain rare cardiac tumors and the nature of ventricular fibrillation. Useful thinking about these and related causes should employ both a horizontal (concurrence of events) and vertical (sequence of events) matrix, in all of which chance plays a major role. One impediment to understanding sudden death associated with coronary disease is the prevalent assumption that one is due to the other without proper examination of the other factors involved, some of which may be more susceptible to intervention or modification. The multifactorial nature of the pathogenesis of sudden death and the recognition that chance is a major determinant of which factors convene and when they will aggregate in the victim are essential elements to consider if more effective means of treatment and prevention are to be obtained.     

Pathogenesis of paroxysmal hypertension developing during and after coronary bypass surgery: A study of hemodynamic and humoral factors

A prospective study of hypertension first appearing during and after saphenous vein bypass coronary surgery was performed in 28 patients to examine the incidence, hemodynamics and mechanism of this problem. In 15 patients (54 percent) new hypertension developed (mean arterial pressure greater than 107 mm Hg), characterized by increased peripheral vascular resistance and unchanged cardiac output within 1 hour after surgery. These 15 patients had a longer history of angina of greater severity, but also had relatively well preserved ventricular myocardium. Because plasma renin activity was depressed in patients in the hypertensive group, activation of the renin-angiotensin system was not important in the pathogenesis of this postoperative hypertension. The expected decrease in total peripheral resistance at the onset of cardiopulmonary bypass was observed in all patients, but later during bypass the peripheral resistance increased in all patients in association with a rise in plasma epinephrine levels. Patients who had hypertension postoperatively had a greater increase in arterial pressure and total peripheral resistance during cardiopulmonary bypass than did those with normal postoperative blood pressure. An elevation in plasma epinephrine and norepinephrine concentration, suggesting enhanced sympathoadrenal responsiveness to the challenge of cardiopulmonary bypass, was characteristic of the hypertensive group. This evidence of enhanced sympathetic activity during surgery may be a useful predictor of the development of postoperative hypertension.     

Sudden death while driving: Role of sinus perinodal degeneration and cardiac neural degeneration and ganglionitis

A young business executive was seen to slump over his steering wheel while driving, after which the automobile veered and turned over. Quickly taken unconscious to a nearby emergency room, he was pronounced dead on arrival. Because there was insufficient physical injury found to account for his death, and because atrial fibrillation had been detected for the first time on a routine physical examination 3 months previously, special examination of the cardiac conduction system was performed. A fibroma was present on the right side of the central fibrous body above the His bundle, similar to several fibromas on the mitral valve. Small foci of neuritis were present in the ventricular myocardium and the atrioventricular node. More extensive neural degeneration and ganglionitis were found near the sinus node, which also exhibited an encircling perinodal flbrosis. Ways in which these abnormalities could have caused a fatal electrical instability of the heart are discussed. Careful examination of the cardiac conduction system is warranted in other fatal automobile accidents under similar circumstances.     

Anatomy of the crista supraventricularis: its importance for understanding right ventricular function, right ventricular infarction and related conditions

During careful studies of the human cardiac conduction system the anatomy of the crista supraventricularis is an inescapable concomitant demonstration. For the purpose of this report the observations from about 1,000 human hearts were combined with special additional studies of 75 human hearts (50 adults, 25 infants), 30 dogs and 5 chickens. The crista supraventricularis is similar in human and canine hearts. Avian hearts differ from mammal hearts in that they contain only a muscular right atrioventricular valve which replaces the crista supraventricularis. In addition to dividing the inflow and outflow pathways of the right ventricle, the crista supraventricularis is crucially located to join the interventricular septum and left ventricle to much of the right ventricular free wall, thereby playing an important role in emptying the right ventricle and closing the tricuspid valve. On the basis of these observations, the function of the crista supraventricularis is examined relative to right ventricular systole, right ventricular infarction, various electrophysiologic problems, the performance of cardiac surgery and new questions in cardiac imaging.     

Experimental studies on the pathogenesis of asystole after verapamil in the dog.

The effect of verapamil on automaticity and conduction in the atrioventricular (A-V) junctional region was studied in anesthetized dogs. In five normal dogs verapamil, 10 microgram/ml, was selectively perfused into the A-V nodal artery and caused first degree heart block, which progressed to second degree heart block in three of the five. Higher concentrations of verapamil, 25 microgram/ml, caused complete heart block in three of five other dogs, but no episodes of asystole (defined as a ventricular pause of 10 or more seconds). In six other dogs after beta receptor blockade with propranolol, 20 microgram/ml, perfused into the A-V nodal artery, verapamil, 10 microgram/ml, regularly caused second degree heart block; in four of the six dogs there was a transient episode of third degree A-V block, and in two of these there was a period of asystole. In each of the 10 dogs pretreated with reserpine, verapamil, 10 microgram/ml, caused third degree A-V block; in seven of these there was a period of asystole with ventricular standstill up to 30 seconds. Concentrations of verapamil that do not produce high grade heart block in the normal heart thus readily cause both high grade block and prolonged ventricular standstill after elimination of adrenergic influences in the A-V junction.     

Coronary anatomy and arteriography in patients with unstable angina pectoris.

A prospective series of 188 patients with the syndrome of unstable angina pectoris undergoing coronary arteriography was reviewed to determine the spectrum of anatomic coronary artery disease, suitability for coronary revascularization and in-hospital morbidity and mortality. Thirty-two patients demonstrated normal to moderately diseased coronary arteries. None of these patients sustained myocardial infarction or died. Twenty patients (10.6 percent) had normal coronary arteriograms. Of the 156 patients having severe coronary artery disease (greater than 70 percent stenosis), 20 patients (13 percent) had left main coronary artery disease. One hundred forty-two patients (91 percent) were potential candidates for coronary surgery; 14 were not candidates because of distal vessel disease or poor left ventricular function. During cardiac angiography or in the subsequent hospital period 12 patients sustained a myocardial infarction and 7 of these died. Of these seven, six had left main coronary artery disease and one had three vessel disease. In three patients who died (1.9 percent of those with severe coronary artery disease) the death may have been related to cardiac catheterization because evidence of myocardial necrosis began within 24 hours of study. Thus, patients with the syndrome of unstable angina pectoris usually presented with severe coronary artery disease and were candidates for coronary revascularization. The anatomic severity of coronary artery disease appeared to be the most important factor contributing to myocardlal infarction or death after cardiac catheterization. Mortality after catheterization was primarily associated with left main coronary artery disease.     

Elevated catecholamines during cardiac surgery: consequences of reperfusion of the postarrested heart

This study determines whether reperfusion of the heart with elevated blood levels of epinephrine (E) and norepinephrine (NE) during cardiac surgery produces deleterious effects. The study was conducted in 60 patients undergoing coronary artery bypass surgery. Arterial catecholamine values increased significantly (p less than 0.05), from prebypass control levels of 152 +/- 29 and 327 +/- 30 pg/ml of E and NE, respectively, to 415 +/- 78 and 554 +/- 49 pg/ml, at initiation of perfusion of the heart after the aortic cross-clamp was removed. Serial measurement of arterial (A) and coronary sinus (CS) E, NE, potassium, lactate, PO2 and CK-MB revealed that during 10 minutes of reperfusion the heart extracted E (positive A-CS difference, p less than 0.05), but that the NE A-CS difference was 0. The CS effluent contained significantly (p less than 0.05) higher concentrations of potassium, lactate and CK-MB during reperfusion than before aortic occlusion. There was no significant correlation of arterial E and NE, CS E and NE or A-CS differences in E and NE with myocardial release of lactate, potassium or CK-MB. There was a weak association (r = 0.4, p less than 0.01) between coronary sinus CK-MB and aortic occlusion time. Maximal arterial E and NE values did not correlate with 10-hour postoperative (maximal) CK-MB values. These results indicate that reperfusion of the postarrested ischemic heart with high levels of endogenously released catecholamines does not worsen ischemia or contribute significantly to myocardial damage.     

Isosorbide dinitrate for the relief of severe heart failure after myocardial infarction.

Severe congestive heart failure secondary to myocardial infarction remains a difficult management problem. Although intravenous vasodilators and mechanical assist devices have been reported to improve the depressed hemodynamic function, these interventions are limited to the intensive care unit and cannot be used for long-term management. This study evaluates the hemodynamic and symptomatic response to sublingual administration to isosorbide dinitrate (5 to 10 mg) in seven consecutive patients with severe congestive heart failure after anterior wall myocardial infarction. Serial measurements of mean right atrial and pulmonary arterial end-diastolic pressure, mean blood pressure, heart rate and cardiac output were obtained during the control period and during the 4 hours after administration of isosorbide dinitrate. The peak response occurred approximately 30 minutes after drug administration with an 83 percent reduction in mean right atrial pressure (from 6 to 1 mm Hg, P less than 0.02), a 36 percent reduction in pulmonary arterial end-diastolic pressure (from 25 to 16 mm Hg, P less than 0.0001) and a 6 percent reduction in mean blood pressure (from 94 to 88 mm Hg (P less than 0.05). There were small but statistically not significant increases in cardiac index (from 2.3 to 2.6 liters/min per m2 and stroke work index (from 26 to 32 gm/beat per m2). The total systemic vascular resistance was reduced by 5 percent from 1,605 to 1,518 dynes sec cm-5 (P less than 0.10). The baseline heart rate of 105 beats/min was not significantly changed. The reduction in pulmonary arterial end-diastolic pressure became statistically significant (P less than 0.05) between 15 and 30 minutes after administration of isosorbide dinitrate and remained significant for 3 to 4 hours. This reduction of pulmonary arterial end-diastolic pressure to less than 22 mm Hg was associated with relief of the patients' pulmonary symptoms. The response to nitroglycerin (0.4 mg) was similar in magnitude but of much shorter duration (approximately 15 minutes for nitroglycerin versus 4 hours for isosorbide dinitrate in patients with and without congestive heart failure. The slope (calculated by dividing the change in cardiac index or stroke work index by the change in pulmonary arterial end-diastolic pressure) was significantly (P less than 0.05) depressed in the patients with congestive heart failure. These data demonstrate that the symptomatic pulmonary venous hypertension can be effectively relieved by isosorbide dinitrate without further compromising left ventricular function.     

Prospective randomized trial of glucose-insulin-potassium in acute myocardial infarction. Effects on myocardial hemodynamics, substrates and rhythm.

Fifty consecutive patients admitted within 12 hours of the onset of symptoms of acute myocardial infarction were randomly assigned to treatment with intravenous glucose-insulin-potassium infusion (23 patients) or to a control group (0.5 N sodium chloride infusion) (27 patients). The glucose-insulin-potassium infusion consisted of 30 g glucose, 50 U regular insulin and 80 mEq KCl per liter infused at 1.5 ml/kg per hour for 2 days. Serial measurements were made of pulmonary arterial end-diastolic pressure, cardiac index, daily fluid intake and output, serum glucose, potassium, urea nitrogen, free fatty acids, osmolarity, creatine kinase-MB isoenzyme and cardiac rhythm. Although all patients admitted comatose died (three glucose-insulin-potassium recipients, one control subject), hospital mortality in patients admitted noncomatose was 0 percent (0 of 20) in glucose-insulin-potassium recipients versus 12 percent (3 of 26) in the control group (three deaths secondary to late pump failure). Glucose-insulin-potassium recipients experienced 4.9 ± 1.3 hours of three or more premature ventricular complexes/min compared with 11.1 ± 1.9 hours for control subjects (P < 0.02). Twelve control patients had 60 episodes of ventricular tachycardia compared with seven glucose-insulin-potassium recipients, who had 12 episodes of ventricular tachycardia. During glucose-insulin-potassium infusion, fluid intake and output, serum glucose and potassium were significantly increased compared with values in control subjects, blood urea nitrogen and free fatty acids were decreased, whereas osmolarity, pulmonary arterial end-diastolic pressure and cardiac index did not differ significantly from control values. Creatine kinase-MB infarct size averaged 124 ± 15 IU/liter in glucose-insulinpotassium recipients and 109 ± 14 IU/liter in control subjects (difference not significant).These data demonstrate that, in patients with acute infarction, glucose-insulin-potassium infusion (1) does not adversely alter hemodynamics, (2) reduces free fatty acids, (3) diminishes frequency of ventricular arrhythmias, but (4) has no demonstrable effect on infarct size as assessed with creatine kinase isoenzyme values. In this ongoing randomized clinical trial, the number of patients studied is too small to permit definite conclusions to be reached regarding the effect of glucose-insulin-potassium infusion on hospital survival.     

Pulmonary arterial compression syndrome caused by false aneurysm of left ventricular outflow tract

A 29 year old man experienced exertional dyspnea and coughing 3 1/2 years after insertion of a Braunwald-Cutter aortic valve prosthesis. Clinical examination suggested pulmonary arterial hypertension, and cardiac catheterization revealed a saccular lesion apparently arising from the left ventricular outflow tract and producing compression of the right pulmonary artery. Origin from the left ventricular outflow tract just under the aortic ring was confirmed at operation. The lesion apparently arose from an anular excavation related to previous endocarditis with abscess formation. Reported cases of similar aneurysmal lesions are briefly reviewed, and other known causes of the pulmonary arterial compression syndrome are discussed.     

Enhanced evaluation of treadmill tests by means of scoring based on multivariate analysis and its clinical application: A study of 608 patients

Six hundred eight patients being evaluated for chest pain who did not have valvular disease, cardiomyopathy, left ventricular hypertrophy or bundle branch block, and were not receiving digitalis, had treadmill tests and coronary angiograms. In 351, various exercise variables were correlated by multivariate analysis to coronary artery disease (CAD). In men, significant variables were: (1) maximal heart rate achieved <80% of maximal predicted heart rate (Mx PHR), (2) ST-T change ≥1 mm, (3) age ≥55 years and (4) treadmill time (TT) <8 minutes. These variables rated diagnostic scores of 9, 6, 5 and 3, respectively. A score of ≥7 was considered diagnostic of CAD. In a test group of 192 men in which ST-T change was compared with treadmill score, sensitivity was 65 versus 85%, specificity 79 versus 74% and accuracy 69 versus 83%.

In women, maximal heart rate <90% of Mx PHR and TT of <6 minutes were significant, with an accuracy of 75%. Moreover, 89% of incomplete tests and 70% of tests in patients with previous myocardial infarction were also correctly diagnosed, This method allows convenient use of significant exercise variables for clinical purposes with improved results.     

Clotted hemopericardium with the hemodynamic characteristics of constrictive pericarditis

Cardiac catheterization in a patient 4 weeks after coronary arterial bypass surgery demonstrated the typical hemodynamic findings of constrictive pericarditis, which completely resolved after removal of 500 ml of clotted pericardial blood. The pericardium was not responsible for the findings because it was left in place. This case demonstrates that clotted hemopericardium may mimic constrictive pericarditis.     

Quantitative coronary arteriography. Coronary anatomy of patients with unstable angina pectoris reexamined 1 year after optimal medical therapy

The effect of optimal medical therapy on coronary arterial anatomy was evaluated in 25 patients with unstable angina pectoris. Coronary arterial diameter and the extent of stenosis were exactly quantified in two successive coronary angiograms performed in each patient at approximately a 1 year interval (range 4 to 31 months, average 12.4 months). The measuring device was a vernier caliper with an accuracy of 0.05 mm. After 1 year of medical treatment 69 stenoses of the three major coronary branches showed no significant change: The average degree of area obstruction of 27 stenoses of the right coronary artery was 79 and 84 percent in the initial and second studies, respectively; that of 26 stenoses of the left anterior descending artery 78 and 77 percent, respectively, and that of 16 stenoses of the left circumflex artery 73 and 83 percent, respectively. In 11 patients, 14 stenoses showed a distinct progression of more than 20 percent area obstruction. All six stenoses showing more than 90 percent obstruction in the first angiogram progressed to complete obstruction within 1 year. In five other patients area obstruction in five stenoses regressed by more than 20 percent. The anatomy of vessel segments distal to obstructions remained unchanged within 1 year. It is concluded from these quantitative measurements that the distribution and severity of coronary lesions are similar in patients with stable and unstable angina pectoris. Coronary anatomy showed no significant change after 1 year of medical treatment. The rate of progression was substantially lower than previously reported in patients with stable angina pectoris.     

Torsade de pointes: the long-short initiating sequence and other clinical features: observations in 32 patients

The clinical setting, precipitating factors, electrocardiographic features and response to treatment of 32 patients with torsade de pointes were reviewed. Thirty-one patients had underlying cardiac disease and 30 patients had a previous underlying cardiac arrhythmia. Antiarrhythmic medications, often in association with electrolyte abnormalities (such as hypokalemia and hypomagnesemia) were the most common precipitating factors. In 22 of 26 patients, the serum drug levels of the antiarrhythmic agents were found to be within the therapeutic range. However, before the administration of agents known to prolong the QT interval, 20 of the 32 patients had, either alone or in combination, baseline prolongation of the QT interval, hypokalemia or hypomagnesemia. All patients had QTc interval prolongation (mean 0.59 second) immediately before the development of torsade de pointes. Marked lability of T wave morphology was frequently noted. Cardiac pacing was the only consistently effective mode of therapy. A characteristic long-short ventricular cycle length as the initiating sequence was found in 41 of 44 episodes of torsade de pointes. Reported data support the high frequency of this electrocardiographic feature of torsade de pointes in which its onset could be analyzed. It is suggested that this electrocardiographic characteristic will aid in both establishing the diagnosis of torsade de pointes and distinguishing it from other polymorphic forms of ventricular tachycardia.     

Incidence of new pulmonary perfusion defects after routine cardiac catheterization.

The incidence of pulmonary perfusion defects after routine cardiac catheterization was assessed in 57 patients by comparing ventilation-perfusion lung scans obtained before and 1 day after catheterization. Patients were prospectively randomized to two groups, one in which right heart catheterization was performed using an antecubital venous cutdown procedure and one in which the percutaneous femoral vein approach was used. Seven patients (12 percent) had new postcatheterization perfusion defects consistent with pulmonary emboli. These patients did not differ significantly from patients without new defects in clinical characteristics, duration of catheterization, hemodynamic variables or route of right heart catheterization. The data suggest that pulmonary embolism may be a more common complication of routine cardiac catheterization than previously appreciated.