Development of an experimental preparation aided to investigate arrhythmogenic and antiarrhythmogenic factors influencing incidence of spontaneous and yet predictable ventricular arrhythmias is described. Using the isolated perfused guinea-pig heart and a system for quantitating rhythm disturbances based on computer-aided statistical analysis of beat-to-beat intervals, a number of factors influencing the incidence of rhythm disturbances were investigated. Manipulation of perfusate composition revealed that, after 'moderate' ischaemia, reperfusion arrhythmias were increased in the presence of noradrenaline and non-glucose fuels. Free fatty acids, unless in the presence of catecholamines, were not particularly arrhythmogenic. In contrast, the presence of pyruvate or lactate, endproduct inhibitors of glycolysis, significantly increased incidence of reflow rhythm disturbances. The dose-dependent arrhythmogenic effects of pyruvate and anti-arrhythmogenic effects of glucose support the thesis that inadequate glycolytic flux could be important in the development of arrhythmias.
Hydralazine (Apresoline) was used to increase heart rate in 21 patients (14 hypertensive and 7 normotensive) suffering from symptomatic sinus bradycardia (SSB). Patients were assessed clinically and by 24-h ECG analysis before and after tailored increasing doses of the drug. Heart rates measured were resting (basal) rate, minimum rate during sleep, maximal rate during the day, and mean rate during the 24-h period (from hourly strips). The longest sinus pause or period of sinus arrest (when present) was also measured. Hydralazine ameliorated symptoms and produced a 20% or greater increase in heart rate in just under two-thirds of the hypertensive and half of the normotensive patients. Blood pressure decreased slightly in hypertensive but not in normotensive patients, and there were no important side-effects. Hydralazine appears to be a useful and effective drug to increase heart rate in patients with SSB.
Lorcainide hydrochloride given at the doses of 150 mg i.v. proved to be well tolerated at the acute stage of a myocardial infarction; the subjective signs were benign and never prevented us from completing the injection. The haemodynamic changes reflect some depressive effects on the myocardial function. Most of the observed changes are transient, and when significant from the statistical point of view, they remain very mild: the cardiac output decreased from 3.4 to 3.2 l/min per m2, the stroke index from 46 to 41 ml/m2, the pulmonary wedge pressure increases from 6.6 to 8.4 mm Hg (mean values). Lorcainide hydrochloride may thus be used as an antiarrhythmic drug in acute myocardial infarction.
Cardiac programmed stimulation in the control of tachyarrhythmias offers encouraging prospectives. We describe two devices which utilize radiofrequency as a means of synchronization and stimulation and can be triggered by the patient himself when tachycardia occurs. In addition we introduce a third anti-tachycardia device, completely automatic, which can be used in cardiologic departments. The first device described permits critical stimulation and can be programmed to deliver a single or double synchronized impulse. The second device, which utilizes the same implanted unit and electrode as used for critical stimulation, when activated searches the tachycardia interruption zone by scanning. The third device, based on the same principles, has a rate discriminator that activates the scanning stimulation. We treated 12 patients: 8 suffering from paroxysmal supraventricular tachycardia (4 with Wolff--Parkinson--White syndrome, 2 with intranodal reentry, 2 with brady--tachy syndrome); 2 patients with ventricular recurrent tachycardia; 1 with atrial flutter; and another with iterative junctional tachycardia. The follow-up varied for every patient from 6 yr to 3 mth.
3 patients with atrial fibrillation, of varying origin, have been successfully converted to sinus rhythm by D.C. shock while on the antiarrhythmic drug amiodarone. D.C. shock did not cause rhythm disturbance. D.C. conversion may not be contraindicated in patients taking amiodarone.
The pulsed Doppler echocardiography (PDE) was used to evaluate the character of mitral valve flow in a large atrial tumor. The tumor obstructed the mitral orifice during diastole. PDE findings, however, showed normal triphasic diastolic flow within the actual mitral orifice and no changes typical for mitral stenosis. The same turbulence pattern as in mitral stenosis was detected in the left ventricle. In addition, PDE revealed the presence of mild mitral regurgitation in agreement with angiography.
Electrophysiologic and histopathologic correlation has been carried out in a patient with scleroderma heart disease, affected by syncopal seizures, who died of recorded ventricular fibrillation. The electrophysiological investigation disclosed dysfunction of sinoatrial conduction, revealed by sinoatrial blocks and by an abnormal return cycle pattern after premature atrial beats. Atrial effective and functional refractory periods were increased and an unusual 'pseudo-Wenckebach' phenomenon between artificial stimulus and atrium was observed during atrial pacing. Intra-AV nodal conduction time was at normal upper limits and Wenckebach-type AV block was obtained on pacing the atrium at 100 beats/min. HV conduction was moderately prolonged in the presence of left anterior hemiblock. The histopathologic substrates of these electrophysiologic disturbances were fibrosis of the sinus node, disrupted internodal pathways and atrio-AV nodal connections, and left bundle branch atrophy. As far as fatal tachyarrhythmia is concerned, myofibrillar degeneration may have contributed to its pathogenesis. It is suggested that both lesions of the ordinary myocardium and specialized conduction system account for the electrical instability of sclerodermic patients.
Previous studies have shown a significant relationship between the clinical effect of digoxin and a tissue response, namely the inhibition of 86Rb uptake by the patients' erythrocytes. In the present study, this relationship is confirmed in patients, in heart failure with sinus rhythm. The slowing of the heart rate but not the QS2 index changes correlates significantly with the 86Rb uptake inhibition.
Na+,K+-ATPase activity was assessed indirectly in three groups of subjects of differing age, and in a group of patients with renal failure, by measuring the 86-rubidium uptake in the patients' own erythrocytes. The inhibiting action of digoxin on this activity was also measured in vitro. Erythrocyte 86Rb uptake was found to be lower in the elderly as was the calculated volume of distribution of digoxin. Sensitivity to the inhibiting action of digoxin increased with age. In the renal failure group 86Rb uptake was diminished and the sensitivity to digoxin was variable. This suggested that Na+,K+-ATPase activity could be one determinant of the volume of distribution of digoxin and that quantitative and qualitative changes of this enzyme could explain features of the pharmacokinetics of digoxin in renal failure and in old age.
Measurements of plasma pancreatic polypeptide and gastrin are reported for the first time in patients with acute myocardial infarction and compared with clinical signs of vagal or sympathetic overactivity. Pancreatic polypeptide concentrations were assessed as an index of vagal activity, but elevated values of pancreatic polypeptide found in 7 of the 13 patients on admission did not correlate with clinical evidence of vagal overactivity. The mean pancreatic polypeptide concentrations were not higher in patients with clinical vagal overactivity than in patients with clinical sympathetic overactivity during the 12 h after the onset of symptoms of acute myocardial infarction. Mean gastrin levels were significantly higher on admission and at 4, 5, 6 and 8 h after the onset of infarction in the patients with clinical features of sympathetic overactivity than in the patients with clinical vagal overactivity. Thus plasma gastrin warrants further assessment as an index of sympathetic overactivity in acute myocardial infarction.
The authors compare the effects of beta-blockers without intrinsic sympathetic activity (ISA) (propranolol, 160 mg/day), moderate ISA (acebutolol, 800 mg/day) and high ISA (pindolol, 20 mg/day). The sinus rate decreases more with propranolol than with acebutolol, during the day (P less than 0.01) and during the night (P less than 0.001), whereas pindolol does not change the daylight rate and increases the nighttime rate (P less than 0.001). The ventricular rate during atrial fibrillation (AV nodal transmission) is modified as is sinus rate. There is no significant difference between propranolol and acebutolol, and a highly significant difference between pindolol and propranolol (P less than 0.001) or acebutolol (P less than 0.01). Moreover, the eurythmic effect of beta-blockers, making RR intervals more regular, is maximal with propranolol and minimal with pindolol, as judged on RR interval histograms. The ISA of the beta-blockers is of major importance for the clinical use of these drugs, and in the case of SA or AV node dysfunction ISA can be useful, but it can obscure the beneficial effects of beta-blocking therapy.
The protective effect of hydroxymercurifluorescein (Mercurascan, MSC) on the ischemic myocardium was evaluated in dogs. MSC was given 17 min after ligation of the descending branch of the left coronary artery in closed-chest animals. The favorable effect of this drug was confirmed (1) by an immediate decrease of ST-segment elevation in electrograms from epicardial electrodes, (2) by a reduced number of Q waves 24 h after the ligation, and (3) by the preservation of CPK activity in the sites with moderate early ST-segment elevations. Microscopic examination also confirmed this. We conclude that MSC given shortly after coronary artery occlusion in dogs protects some cells in the border zone of ischemic focus from the development of necrosis. The membrane stabilizing effect or neutralization of proteolytic enzymes are the suggested explanations for the mechanism of MSC action.
The effect of hyperbaric oxygen (HBO) on infarct size associated with myocardial infarction remains uncertain. Accordingly, the present study was performed in 46 conscious dogs with experimental infarction to determine the effect of HBO on enzymatic estimates of infarct size. Since HBO may affect plasma creatine kinase (CK) release or disappearance, parameters used to calculate enzymatic estimates of infarct size from plasma CK, we assessed infarct size by directly measuring myocardial CK depletion. Twenty-three animals were given HBO (2 atm of pressure) for 3 h immediately after coronary occlusion and results of infarct size compared to those in 23 dogs with occlusion who remained in room air. In 10 other animals CK release was measured after coronary occlusion in 5 controls and compared to 5 treated. In 5 normal animals the CK disappearance rate of purified canine CK was determined before and after HBO. Infarct size was determined 24 h after coronary occlusion and in the treated animals averaged 25.4 +/- 1.3% of LV (mean +/- SEM), and being similar to controls (26.7 +/- 1.4, P greater than 0.25). The plasma CK disappearance rate before and after HBO was the same being 0.0072 +/- 0.0022 (min-1) and 0.0073 +/- 0.0021, respectively. Total CK released into the plasma was also the same in treated and controls (2232 +/- 210 IU and 2011 +/- 232), as was the ratio of CK released to that depleted from the myocardium (0.15 +/- 2% vs 0.15 +/- 3%). Our results indicate: (1) HBO does not reduce infarct size produced experimentally in the conscious dog; (2) HBO does not affect CK release or disappearance; and (3) estimates of infarct size by plasma CK remain valid despite administration of HBO.
The pharmacodynamic effects (changes of systolic time intervals, STI, reaction of pulmonary arterial pressure) of digitoxin were studied in 7 patients with severe congestive heart failure in comparison with the corresponding plasma level. STI indicated glycoside-dependent changes, i.e. shortening of LVETc and QS2c and normalization of prolonged PEPc, while ICT shortening was less observed. In 2 patients with cor pulmonale a pulmonary oedema occurred accompanied with prolonged LVETc. During the early period of glycoside-dependent recompensation no significant correlation between STI shortening and glycoside plasma level was observed. Because of the retarded normalization of the haemodynamics of the pulmonary circulation and because of possible side-effects, rapid digitalization has to be reconsidered.
The effect of slow-release nitroglycerin and nitroglycerin ointment in reducing anterior myocardial infarction size was assessed in 18 patients by means of epicardial mapping. The sum of all ST elevations (sigma ST), the number of leads with ST elevations greater than 1 mm (NST), the sum of the ST segment elevations of those leads with ST elevations greater than 1 mm (sigma STmm) and the average ST segment elevations (ST) were evaluated. No statistically significant difference between the two forms of nitroglycerin and placebo was found over a 72-h period. These data suggest that no benefit in terms of reduction in myocardial infarction size, assessed by epicardial mapping, is obtained from therapy with oral slow release nitroglycerin and nitroglycerin ointment.
The effects of changes in posture on left ventricular (LV) diameter and function were studied by echocardiography in 14 healthy children. On changing from the supine to the standing position, enddiastolic LV diameter decreased by 13 +/- 5% (P < 0.001), heart rate increased (P < 0.05) and calculated stroke index (-37 +/- 11%, P < 0.001) and cardiac index (-32 +/- 14%, P < 0.001) fell. There was not a significant change in the echocardiographic measurement. % delta s, mean Vcf and max Vpwm (ns) but mean Vcf increased in relation to mean blood pressure in 3 patients, suggesting an increase in LV contractility. Squatting was accompanied by an increase in LV cavity dimension (P < 0.001), while heart rate fell slightly and calculated stroke index (%35 +/- 28%, P < 0.001) and cardiac index (+33 +/- 27%, P < 0.001) increased. Mean blood pressure increased by 19 +/- 18% (P < 0.01). There was again no significant change in % delta s, mean Vcf and max Vpwm. Most patients fell on the control (supine) blood pressure--mean Fcf curve; in 2 patients there was a residual increase in sympathetic tone and LV contractility.
M-mode echocardiography was performed in 20 asymptomatic patients undergoing chronic hemodialysis, in order to assess pericardial involvement. Six of the patients had small to moderate amounts of pericardial effusion. One of these patients and 5 others showed an echocardiographic pattern of pericardial thickening. No correlation was found between pericardial involvement and age, sex, secondary hyperthyroidism, serum levels of urea, creatinine or uric acid. The traditional diagnostic techniques commonly used for the detection of pericardial disease such as physical examination, chest X-ray and electrocardiography were not helpful in our patients. Our study demonstrates the high incidence of pericardial involvement in asymptomatic chronically dialyzed patients. Periodic echocardiographic evaluation is recommended for assessment of the presence and significance of these findings.
