Metabolism of free fatty acids, glucose and catecholamines in acute myocardial infarction: Relation to myocardial ischemia and infarct size

The myocardial metabolism of free fatty acids, glucose and catecholamines is reviewed in relation to current trends in the therapy of experimental myocardial infarction. Major modifications in the metabolism of free fatty acids, glucose and catecholamines have already been found after acute myocardial infarction in man, and animal experimental data suggest that such metabolic changes might play a role in the modification of infarct size and sometimes in the development of arrhythmias. However, animal experiments often represent extreme situations and the therapeutic use in man of agents to modify the metabolism of free fatty acids, glucose or catecholamines after myocardial infarction needs intensive investigation before general application. The sum total of the evidence from animal experiments suggests that increased circulating concentrations of free fatty acids and catecholamines, if sufficiently high, may be harmful rather than helpful to the outcome of acute myocardial infarction, and that increased provision of glucose (as glucose, insulin and potassium) may be beneficial. Reservations to these conclusions are that the concentrations used appear to be important factors in catecholamine and free fatty acid effects, and that the mechanism of action of glucose-insulin-potassium is more complex than originally thought.     

Left ventricular bypass using a cardiac allograft: Hemodynamic studies

Human allograft bypass of the failing left ventricle is an efficient and practical way of effecting short-term improvement in the overall hemodynamic status of patients. It is suggested that controlled sequential pacing of the donor heart would improve the overall hemodynamic result and better preserve function of the bypassed ventricle. Simultaneous bypass of the right ventricle might prevent the acute right heart failure seen during serious ventricular arrhythmias occurring in the recipient heart. Future indications for the technique in modified form could include severe biventricular failure and acute reversible forms of heart failure.     

Biochemical aspects of arrhythmogenesis and ventricular fibrillation.

The problem of arrhythmogenesis in acute myocardial infarction is approached by an analysis of the biochemical and metabolic factors causing abnormalities in the cardiac action potential. A fundamental change in acute ischemia is the abrupt increase in extracell potassium occurring within seconds of coronary occlusion. Localized hyperkalemia not only causes loss of resting membrane potential and shortening of the action potential duration but also can block the fast inward current to unmask the slow channel. If hyperkalemia is sufficiently severe, then normal phase 0 depolarization cannot occur. In such conditions, a slow response can be provoked by catecholamine activity, the cell effects of which are thought to be mediated by cyclic adenosine monophosphate (AMP). Increased cyclic AMP in ischemic tissue is circumstantially linked to the onset of ventricular arrhythmias and fibrillation after coronary occlusion in baboon, cat and pig preparations. More direct evidence for an arrhythmogenic role of cyclic AMP is provided by the demonstration in an isolated heart preparation of a decrease in the ventricular fibrillation threshold by perfusion with exogenous dibutyryl Cyclic AMP or by an increase in tissue cyclic AMP by beta agonists or theophylline, or both. Glycolytic adenosine triphosphate appears to play a special role in the maintenance of the action potential duration because lactate, free fatty acids or inhibition of glycolysis all shorten the action potential duration. Glucose is the substrate best able to maintain the action potential duration during hypoxia.Increased automaticity occurs in partially depolarized Purkinje fibers, especially when there is stimulation by catecholamines or cyclic AMP in the presence of a low external potassium level. These and other metabolic factors are thought to play an important role in the genesis of ischemic arrhythmias. An understanding of these effects contributes significantly to the elucidation of the mode of action of antiarrhythmic drugs. It remains to be determined whether the hypotheses derived from a variety of animal models can be extrapolated to the very complex setting of ischemic heart disease in man.     

Congenitally corrected transposition of the great vessels: Localization of the site of complete atrioventricular block using His bundle electrograms

Complete atrioventricular block proximal to the bundle of His in a patient with congenitally corrected transposition of the great vessels was documented using His bundle electrograms. The spontaneous rhythm probably originated from the bundle of His and was responsive to carotid sinus massage, atropine and isometric and treadmill exercise. These electrophysiologic observations are consistent with recent anatomic studies of congenitally corrected transposition of the great vessels.     

The value of warning arrhythmias in the prediction of ventricular fibrillation within one hour of coronary occlusion. Experimental studies in the baboon

Factors associated with the development of ventricular fibrillation after coronary artery ligation were studied in a subhuman primate (Cape Chacma baboon). In 25 or 66 per cent of 38 baboons, primary ventricular fibrillation occurred within the first hour after the onset of acute myocardial infarction. Increasing age, total heart weight, and the size of the infarct were directly related to the incidence of primary ventricular fibrillation. Anterolateral infarcts had the highest risk of ventricular fibrillation. Anteroseptal and posterior infarcts had the best survival rate for the first hour. Male baboons were more prone to develop ventricular fibrillation than were females. There was no definite progression from ventricular ectopic beats to ventricular fibrillation. In the presence of ventricular tachycardia (even when brief in duration), ventricular bigeminy, or R-on-T beats, ventricular fibrillation has to be expected from the time of onset of the arrhythmia till 30, 20, or 10 minutes have elapsed, respectively. Beyond these times, ventricular fibrillation did not develop during the experimental period. Conversely, the absence of these signs could predict survival for 1 hour. The over-all efficiency of the warning signs in predicting ventricular fibrillation or survival was 85 per cent. Ventricular fibrillation occurred without any of these 3 warning signs in only 1 baboon (5 per cent of all cases). It is suggested that these warning arrhythmias could have a practical value in the management of patients with acute myocardial infarction of recent onset by anticipating the time of impending ventricular fibrillation.     

Use of a double atrial-triggered standby pacemaker system for a patient with a biventricular bypass heterotopic cardiac homograft.

In a patient who had a biventricular bypass heterotopic cardiac homograft a double atrial-triggered standby pacemaker system was implanted to allow sequential atrial pacing of both hearts. The system design permitted either the recipient or the donor heart to dictate the rate of its fellow, depending on which heart had the faster spontaneous sinus rate at any time. Alternative methods for achieving sequential pacing are discussed.     

Surgical repair of congenitally corrected transposition of the great arteries: Results and follow-up

Eighteen patients with congenitally corrected transposition of the great arteries had open heart repair for intracardiac associated defects. Fourteen patients (78%) are alive during the follow-up period (mean 4.5 years). Seventeen (94%) of the 18 patients had ventricular septal defect closure, and 12 (66%) insertion of a pulmonary artery conduit. Surgical repair of the tricuspid valve was required in 6 patients (33%) during the first operation and in 3 additional patients during a second operation (total 50%). When hemodynamic overload or cardiac compromise was detected after surgery it was directly related to identifiable residual defects such as atrioventricular valvular insufficiency, residual ventricular septal defect, or pulmonary conduit stenosis. Repeat open heart operation for residual defects was common during the follow-up period (8 of 18 patients, 44%). No patient showed primary systemic or pulmonary ventricular dysfunction during the follow-up period. None of the last 11 patients developed complete heart block. Postoperative intraventricular conduction defects were common and are presumably caused by surgical injury of the bundle branches.Our observations suggest that surgical repair of congenitally corrected transposition of the great arteries can be currently achieved with acceptable risk. Improved knowledge of the precise location of the specialized conduction system resulted in a marked decrease in the Incidence of atrioventricular (A-V) block in patients with congenitally corrected transposition of the great arteries undergoing intracardiac repair. In the absence of postoperative residual defects it can be expected that longevity and quality of life will improve considerably, but many of these patients may require a repeat operation.     

Role of beta-adrenoreceptor antagonism in the prevention of reperfusion ventricular arrhythmias: effects of acebutolol, atenolol, and d-propranolol on isolated working rat hearts subject to myocardial ischemia and reperfusion

The role of catecholamines in the genesis of ventricular arrhythmias during the reperfusion period following coronary occlusion remains incompletely understood. An isolated rat heart preparation, free from the influence of autonomic innervation or of circulating catecholamines, was used to assess the effects of beta-adrenoceptor blockade. The hearts were prelabeled with tritiated norepinephrine ( NE3H ), and the total radioactivity and that in NE3H were measured in the effluent coronary flow. The left main coronary artery was ligated for 10 minutes after which reperfusion followed. The liberation of NE3H and the development of ventricular tachycardia and fibrillation were monitored throughout. The cardioselective beta-antagonist agent, acebutolol, in a high concentration (1.1 X 10(-4)M), had good beta-antagonist effect in response to the added isoproterenol (10(-6)M); this concentration of acebutolol also suppressed sustained reperfusion ventricular arrhythmias but unexpectedly increased the release of NE3H . Atenolol, another cardioselective agent, did not prevent reperfusion ventricular arrhythmias even in a high concentration of 40 mg/L (1.5 X 10(-4)M). The d-isomer of propranolol, with poorer beta-antagonist properties than the l-isomer, prevented such ventricular arrhythmias in a concentration of 1.3 X 10(-5)M, which was low when compared to that of atenolol. It is proposed that the beta-antagonist activity of the compounds tested could not explain the inhibition of reperfusion ventricular arrhythmias and that another quality such as membrane-stabilizing activity may be involved.     

Systemic atrioventricular valve regurgitation in corrected transposition of the great vessels: Angiographic differentiation of operable and nonoperable valve deformities

Abnormalities of the systemic atrioventricular (A-V) valve are frequently present in patients with corrected transposition. Systemic A-V valve regurgitation is usually present and may be amenable to operative correction with valve replacement if the regurgitation is caused by normally positioned but deformed valve leaflets or a dilated valve ring, or both. Systemic A-V valve regurgitation secondary to the more common Ebstein-type malformation of the inverted tricuspid valve is an inoperable condition at present. Displacement of the valve leaflets below the level of the valve ring may be seen in the angiocardiograms of patients with this finding and is the differentiating feature between the two lesions. Ten cases of systemic A-V valve regurgitation in patients with corrected transposition are reviewed to illustrate these features.     

Right and left ventricular function after the Mustard procedure in transposition of the great arteries.

Right and left ventricular function was assessed at cardiac catheterization in 33 asymptomatic patients 0.5 to 11 years (mean 4.6) after the Mustard operation for complete transposition of the great arteries. Ages at operation had ranged from 0.5 to 16 years (mean 4.2 years). Right ventricular function was assessed using videodensitometric determination of ejection fraction and ventricular volume data. Ventricular volumes were obtained by computerized video analysis utilizing Simpson's rule. The right ventricular ejection fraction was 37 +/- 11 percent (standard deviation), as assessed with videodensitometry and 42 +/- 10 percent as assessed with ventricular volume--both values less than normal (P less than 0.001). Right ventricular end-diastolic volume was significantly greater than normal (P less than 0.001) and averaged 202 +/- 70 percent, but left ventricular end-diastolic volume averaged only 125 +/- 53 percent. These observations after the Mustard operation indicate that right ventricular function is seriously decreased with relatively preserved left ventricular function. They support efforts for surgical correction utilizing the left ventricle as the systemic ventricle.     

Supravalvular mitral stenosis associated with tetralogy of Fallot.

The association of tetralogy of Fallot with supravalvular mitral stenosis is a rare anomaly that has been reported only once previously. The difficulty of preoperative diagnosis is emphasized. Although left-sided obstructive lesions in association with tetralogy of Fallot are rare, their recognition is imperative since these are surgically correctable anomalies and potentially lethal, as proved in this case and the one previously reported.     

Permanent pacemaker therapy in corrected transposition of the great arteries: analysis of site of lead placement in 40 patients

A retrospective analysis of 58 pacemaker leads in 40 patients with corrected transposition of the great arteries (CTGA) was made to compare the function of endocardial and epicardial leads. Extensive trabeculations of the normal right ventricle are generally thought to be essential for endocardial pacemaker lead stability. Because the systemic venous ventricle in CTGA lacks an extensive trabecular network, there has been concern that transvenous lead placement may result in a high rate of dislodgement. Epicardial leads have been assumed to be more reliable in these patients. Forty-seven epicardial and 11 endocardial leads were placed in 40 patients with CTGA who required permanent pacemaker therapy for symptomatic bradycardia. Of 13 episodes of epicardial lead malfunction in 158 patient-years, 3 were due to lead fracture and 10 to high thresholds. Surgery was required to correct the lead malfunction in 12 instances and thoracotomy was necessary for new lead placement in 6 patients. During 26.2 patient-years, there were 2 episodes of endocardial lead failure due to a high acute threshold and perforation. There were no instances of endocardial lead dislodgement. No association between type of failure and lead design was noted for either endocardial or epicardial leads. Actuarial analysis of survival revealed no significant differences in reliability between endocardial and epicardial leads. Endocardial lead fixation in the systemic venous ventricle in patients with CTGA is adequate to prevent lead dislodgement and preferable to epicardial lead placement because thoracotomy is avoided.     

Lack of connection between the atria and the peripheral conduction system in a case of corrected transposition with congenital atrioventricular block

This is the first documented histologic study of the heart of a patient with corrected transposition of the great vessels and congenital atrioventricular (A–V) block with no connection between the atria and an anterior type of peripheral conduction system. Musculature in the superior (anterior) walls of both atria was absent, as was the anterior A–V node. The peripheral conduction system began with the bundle of His. In place of the absent atrial musculature, fibrosis and calcification were present. The relation of laboratory evidence of connective tissue dyscrasia in the mother to the congenital A–V block in the child is discussed.     

Prediction of left ventricular pressure from the vectorcardiogram in transposition of the great arteries

Eighty-two cardiac catheterizations were performed in 72 children with complete transposition of the great arteries; vectorcardiograms (Frank lead) and orthogonal electrocardiograms were obtained in all cases within 24 hours. Fifty-six of these studies were performed in children with an additional ventricular septal defect, and 26 in children with an intact ventricular septum. There was a significant correlation between the ratio of the right and left maximal spatial vectors and the S/R ratio in lead X of the orthogonal lead electrocardiogram. A clockwise loop in the horizontal vector or an S/R ratio of more than 2:1 suggested decreased left ventricular pressure, whereas a counterclockwise or figure-of-8 loop in the horizontal plane or an S/R ratio of less than 2:1 in lead X of the orthogonal electrocardiogram suggested increased left ventricular pressure. Nineteen additional patients with transposition of the great arteries were studied in the same way. With use of the direction of rotation of the horizontal loop and the S/R ratio in lead X, left ventricular pressure was correctly predicted in 84 percent of cases.

After cardiac catheterization has established the diagnosis of transposition of great arteries, repeat vectorcardiograms should be obtained to determine left ventricular pressure. In a patient with initially decreased left ventricular pressure, change to a figure-of-8 or counterclockwise loop or the presence of an S/R ratio in lead X of less than 2.0 suggests the development of a systemic level of left ventricular pressure. This finding is an indication for repeat catheterization.