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Cellular rejection of the conduction system after orthotopic heart transplantation for congenital atrioventricular block.

We report a case of severe acute cellular rejection of the cardiac allograft conduction system in a 15-month-old girl who received orthotopic heart transplantation (OHT) for congestive heart failure from a congenital heart block. Post-operatively, the patient was treated for clinical evidence of rejection, but did not have electrocardiographic findings of heart block. Six weeks after transplantation, the patient developed sudden-onset bradycardia and died. Autopsy showed severe acute cellular rejection involving primarily the conduction system. Cellular rejection of the cardiac conduction system is a potentially lethal complication of OHT. Although diagnostic modalities to predict or detect ongoing cellular rejection in the conduction system are limited, recognizing the early signs, such as post-operative heart block, may prevent devastating consequences.

Bradycardia↗

Decremental atriofascicular accessory pathway with bidirectional conduction: delineation of atrial and ventricular insertion by radiofrequency current application.

A 17-year-old girl with a corrected complex congenital heart disease and recurrent episodes of supraventricular tachycardia was referred for catheter ablation. Electrophysiologic studies revealed the presence of an accessory pathway (AP) with bidirectional conduction and decremental properties. We demonstrated a course parallel to the node-His AV conduction system. Transient abolition of the bidirectional conduction through the AP was obtained by radiofrequency application to the ventricular insertion located in the distal right bundle branch and to the atrial insertion, located in the mid-anterior atrial septum. Radiofrequency application at the low anterior atrial septum, above the His bundle, successfully abolished AP conduction without affecting AV nodal conduction. Demonstration of the course and insertions of the AP, its bidirectional decremental conduction properties, and the association with a complex congenital heart disease are exceptional and interesting findings and raise the possibility of an accessory AV node with a parallel conduction pathway to the right bundle branch.

Adolescent↗

Cyclic adenosine 3', 5'-monophosphate, adenyl cyclase and phosphodiesterase in the conduction system of bovine heart.

Cyclic adenosine 3', 5'-monophosphate (cyclic AMP) and adenyl cyclase and phosphodiesterase activities were determined in the specialized myocardial tissue of the conduction system of bovine heart and then compared with those in the ordinary myocardial tissue. The conduction system was comprised of the atrioventricular node (A-V node), the His bundle and the right and the left bundle branches (RBB and LBB). The content of cyclic AMP was higher in the ordinary myocardial tissue than in the specialized myocardial tissue. In the specialized myocardial tissue, its content was highest in the A-V node and lower in the His bundle than in the LBB and the difference between the contents in the RBB and the LBB was not significant. Adenyl cyclase activity as well as the content of cyclic AMP was higher in the ordinary myocardial tissue than in the specialized myocardial tissue. Its activity was higher in the A-V node than in the His bundle or the RBB, and the activities in the His bundle, the RBB and the LBB were similar. Phosphodiesterase activity was higher in the ordinary myocardial tissue than in the A-V node, and the activities in these 4 sections of the conduction system were similar.

Adenylyl Cyclases↗

[Vasopressin concentration in the blood and sensitivity of the cardiovascular system to it during aging].

With aging the content of the blood vasopressin increases. In old animals smaller doses of vasopressin induce coronary insufficiency (rise of T wave, shift of S-T segment, disorders of the atrio-ventricular conductivity). On continuous administration of vasopressin (during a month), arterial hypertension appears only in old animals due to increase in cardiac output, stroke volume at unchanged cardiac rhythm, and to some decrease in the total peripheral resistance.

Adult↗

Structural differences in the cytoarchitecture and intercalated discs between the working myocardium and conduction system in the human heart.

Working and specialized cardiac myocytes and their intercalated discs in adult human hearts without history of cardiac disease were examined by scanning electron microscopy. The NaOH/ultrasonication treatment of cardiac tissues resulted in the digestion of connective tissue and separation of intercellular junctions. Auricular and ventricular working cardiac myocytes were quasi-cylindrical in shape, bifurcated, and connected end-to-end at the intercalated discs. The intercalated discs in the working cardiac myocytes showed a stair-like profile, consisting of steps (plicate segments) and corresponding risers (interplicate segments). The ventricular myocytes, in particular, had many steps and risers. The plicate segments were filled with numerous finger-like microprojections. The strands of the myocytes in the sinoatrial node were oriented linearly, while those in the atrioventricular node formed a reticular network. The intercalated discs in both nodal cells were underdeveloped, having few microprojections. Myocytes in the atrioventricular bundle (His) and the right limb were arranged in parallel, and were characterized by the presence of slender branches. Purkinje cell strands formed reticular networks. The intercalated discs in the His-Purkinje system were irregular in appearance, and the microprojections were larger in size and smaller in number than those of working myocytes. The myocytes in the crista terminalis and surrounding the fossa ovalis resembled cells in the His-Purkinje system rather than auricular working myocytes in morphology, and may act as the internodal pathway. It is concluded that morphological differences in both the cytoarchitecture and intercalated discs were closely related with contraction and impulse propagation in the various regions of the human heart.

Aged↗

A histological study of the cardiac conduction system in a heifer with complete atrioventricular block.

A case of complete atrioventricular (AV) block of congenital origin in a 16-month-old Holstein heifer was studied histologically with serial sectioning of the cardiac conduction system. The heart was enlarged and showed moderate dilatation of the left and right ventricles. Histologically, the abnormally placed and poorly formed AV bundle was observed in association with abnormality in the tricuspid extension of the central fibrous body, suggesting that the pathological state of the AV bundle had been responsible for the complete AV block. This type of anatomical fault in the AV bundle is considered to be part of an embryological, developmental malformation of the central fibrous body.

Animals↗

Biochemical characterization of the conduction system of the bovine heart.

The enzyme level profiles of some regulatory enzymes and the isozyme patterns of some marker enzymes in bovine adult specialized, adult ordinary and fetal ordinary heart muscles were examined in order to biochemically characterize specialized heart muscle. The activities of hexokinase, phosphofructokinase and glucose-6-phosphate dehydrogenase in adult specialized heart muscle were significantly higher than those in adult ordinary heart muscle, but were similar to those in fetal ordinary heart muscle. The carnitine content and carnitine acetyltransferase activity in adult specialized heart muscle were lower than those in adult ordinary heart muscle. The isozyme patterns of creatine kinase, fructose-bisphosphate aldolase and pyruvate kinase in adult specialized heart muscle resembled those in fetal ordinary heart muscle. These results indicate that adult specialized heart muscle has the biochemical characteristics of fetal ordinary heart muscle.

Animals↗

[Effect of strophanthin and atropine on atrioventricular conduction in acute myocardial infarct].

The effect of single therapeutic doses of strophanthin (0.25--0.4 mg) and atropine (0.75--1,0 mg) on cardiac contraction was studied in 39 patients with acute myocardial infarction and in 12 subjects with no signs of organic heart affection by recording the electrical potentials of the heart conduction system. The indicated dose of strophanthin caused changes in the intervals of the electrogram neither in individuals who did not have myocardial infarction nor in patients with acute myocardial infarction, including those with myocardial infarction complicated by atrioventricular and intraventricular block. Atropine improved atrioventricular conduction by shortening the PH interval in patients with myocardial infarction complicated by I--II grade atrioventricular block and had no marked effect on the spread of excitation impulses along the atrioventricular node in higher grades of atrioventricular block. Atropin shortened the PH interval slightly in individuals without myocardial infarction and in patients with uncomplicated myocardial infarction, but did not have an effect on intraventricular conduction.

Acute Disease↗

The cardiovascular manifestations of systemic sclerosis (scleroderma).

In conclusion, systemic sclerosis is both a fascinating and frustrating affliction. It is a systemic disease of multiple stages. Prognosis is dependent on the site and extent of visceral involvement. There is evidence to implicate the vascular system as the primary target organ of the disease. The cardiovascular manifestations include myocardial fibrosis, pericarditis, and a variety of arrhythmias and conduction abnormalities. Intractable heart failure or sudden cardiac death can ensue. Cardiac involvement in systemic sclerosis portends an ominous prognosis, and is probably most directly related to the extent of myocardial fibrosis which is present. The pathogenesis of myocardial fibrosis has not been determined, but it appears to be a result of an impairment of myocardial perfusion at both the small artery and microvasculature level. Obstructive, vasospastic, and devascularization factors all may be playing a role.

Blood Vessels↗

Effects of hypoxia on the use-dependent inhibition of conduction velocity induced by cibenzoline in guinea pig ventricular myocardium.

The use-dependent effects of cibenzoline, a new anti-arrhythmic drug, on the maximal rate of rise (Vmax) of the action potential and on conduction velocity, and their corresponding recovery kinetics were studied in isolated papillary muscles of guinea pigs under normal and hypoxic conditions. Standard microelectrode techniques were applied to monitor the action potential of the muscles and their conduction. Under control conditions, the amount of use-dependent block of Vmax, conduction velocity, and square of conduction velocity, induced by 10 mumol/L cibenzoline were 26.5 +/- 3.9, 13.8 +/- 1.4, and 25.6 +/- 2.4%, respectively; under hypoxic conditions, these values increased to 32.3 +/- 4.8, 19.7 +/- 1.2, and 35.5 +/- 2.0%, respectively. In the presence of 10 mumol/L cibenzoline, the mean values of time constants for the onset of the use-dependent inhibition of Vmax, conduction velocity, and the square of conduction velocity, during a 2-Hz stimulation, were 3.65 +/- 0.27, 2.77 +/- 0.33, and 2.56 +/- 0.26 seconds, respectively. Under hypoxic conditions, these values changed to 5.10 +/- 0.96, 3.05 +/- 0.44, and 2.84 +/- 0.39 seconds, respectively. The recovery time constants averaged 14.72 +/- 4.08 seconds (for Vmax), 22.23 +/- 3.78 seconds (for conduction velocity), and 23.17 +/- 13.38 seconds (for the square of conduction velocity) in the presence of 10 mumol/L cibenzoline, and 17.19 +/- 8.59 seconds (for Vmax), 15.77 +/- 2.37 seconds (for conduction velocity), and 16.82 +/- 2.61 seconds (for the square of conduction velocity) under hypoxic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of cromakalim, pinacidil and nicorandil on cardiac refractoriness and arterial pressure in open-chest dogs.

The cardiac electrophysiologic effects of the potassium channel activators cromakalim, pinacidil and nicorandil were determined in anesthetized open-chest normotensive dogs using conventional surface electrogram recording techniques. Intravenous administration of cromakalim (0.025-0.5 mg/kg), pinacidil (0.1-2.0 mg/kg) and nicorandil (0.1-2.5 mg/kg) produced large dose-dependent decreases in arterial blood pressure accompanied by smaller reductions of atrial and ventricular effective refractory periods. The shortening of refractoriness was more pronounced in the atrium than in the ventricle and was similar for all three compounds at a given level of hypotension. Effects on other electrophysiological parameters were minimal. Atrial arrhythmias could be induced during electrical pacing at doses of cromakalim and pinacidil producing excessive (greater than or equal to 40%) decreases in mean arterial pressure. No arrhythmias were observed with nicorandil. Induction of the arrhythmias appeared to be closely coupled to the extrastimuli (S2) used to determine refractory periods and was associated with a significant reduction in atrial refractory period (greater than or equal to 30%). No ventricular arrhythmias were observed in this study with any of the compounds tested. Although the plasma levels reached in this study are likely to be higher than those seen clinically, the results nevertheless suggest the potential for cardiac electrophysiologic effects by these agents.

Animals↗

Cardiovascular autonomic reflexes in heavy smokers.

In order to study the effect of smoking on cardiovascular function, 25 healthy subjects with an average smoking history of 25 +/- 9 pack-years were examined using the Valsalva manoeuvre and the deep-breathing test. For each smoker there was a healthy, non-smoking control subject of matching age, sex and body mass index. During the tests, heart rate and blood pressure were recorded continuously. Compared with the controls, the smokers had (1) a smaller increase in heart rate during the strain phase of the Valsalva manoeuvre (P = 0.04); (2) weaker rebound increases in arterial pressure after the Valsalva strain (P = 0.007 for systolic and P = 0.02 for diastolic blood pressure); (3) smaller reflex bradycardia after the Valsalva strain (P = 0.02); and (4) a longer latency between post-strain rises in pressure and bradycardia (P = 0.001). This suggests that diminished blood pressure responses occur as a consequence a chronic dysregulation of peripheral vasoconstriction, while diminished heart rate responses are due to attenuated blood pressure responses. A prolonged latency may be a sign of a dysfunction of parasympathetic baroreflex control. It is concluded that heavy smoking is accompanied by a disturbance of cardiovascular autonomic control.

Adult↗

Transient autonomic dysfunction precedes ST-segment depression in patients with syndrome X.

Increased sympathetic drive has been suggested to play a role in the pathogenesis of syndrome X (angina pectoris, positive exercise testing, and angiographically normal coronary arteries). Heart rate variability (HRV) studies have shown that patients with syndrome X have an imbalance in autonomic nervous system activity (sympathetic predominance). However, it is not known if transient ST-segment depression which occurs in syndrome X during daily activities is related to this autonomic nervous system dysfunction. This study investigates the relation between the response of the autonomic nervous system, as assessed by HRV analysis, and the occurrence of transient ST-segment depression during 24-hour ambulatory electrocardiographic monitoring in 23 patients (4 men and 19 women, mean age 55 +/- 6 years) with syndrome X. The frequency-domain variables of HRV low-frequency (0.04 to 0.15 Hz) and high-frequency (0.15 to 0.40 Hz) power were measured at 6-minute intervals during the 30 minutes preceding the onset of transient ST-segment depression. Fourteen patients (61%) had > or = 1 episode of ST-segment depression in the 24 hours, whereas the remaining 9 patients (39%) had no significant ST-segment change. HRV measures differed according to whether or not ST-segment depression was associated with increased heart rate. Episodes of ST-segment depression associated with increased heart rate were preceded by a reduction of high-frequency power and an increase in the low-frequency--high-frequency ratio, whereas episodes of ST-segment depression not associated with increased heart rate showed no significant HRV changes. Low-frequency power remained unchanged irrespective of heart rate. Thus, in patients with syndrome X, a sympathovagal imbalance (sympathetic predominance due to vagal tone withdrawal) precedes episodes of ST-segment depression that are associated with an increased heart rate.

Autonomic Nervous System↗

Effects of cardiac autonomic imbalance on postnatal changes in the electrocardiographic Q-T interval in conscious swine.

The effects of partial autonomic denervation of the heart rate and Q--T interval were examined during maturation in swine. Four groups of newborns were prepared: right stellate ganglionectomy (RSG), left stellate ganglionectomy (LSG), right cardiac vagotomy (RCV) and sham-operated. Swine were studied postsurgically for eight weeks. Unexpected deaths of unknown cause occurred in five of the 20 denervated swine but in none of the 10 sham-operated controls. Prolongation of the Q--T interval was greatest in RSG animals and least in RCV as compared to controls. The results indicate that we have successfully developed an animal model of a long Q--T syndrome in swine.

Animals↗