Role of histamine in cardiac muscle function--an attempt at demonstrating the presence of intracellular histaminergic H2-type receptors.

BACKGROUND: Histamine is one of the biologically active substances that activate adenyl cyclase enzymatic system through H2 receptor. The aim of the study is demonstration of the presence of membranous histamine receptors in cardiomyocytes and determination of their role in function of the cardiac muscle cell. MATERIAL AND METHODS: The experiments were carried out on 20 rabbits divided into two experimental groups. Electric and mechanical activity of cardiac muscle trabecula was registered by glass microelectrodes' method in group I and by saccharose slit method in group II. RESULTS: In group I after administration of 2.5 microM x l-1 of histamine mean rhythm rate increased to 61 +/- 2.7 stimulations x min-1, contractile tone increased by 55.7 +/- 4.9% in relation to the control values, relaxation time shortened to 139.2 +/- 1.8 ms, while time to pike decreased to 229.6 +/- 2.5 ms. The following effects were observed after administration of 5 microM x l-1 of histamine: mean rhythm rate increased to 76.4 +/- 4.5 x min-1, amplitude of the potentials was unchanged, while their duration shortened to 227.7 +/- 3.2 ms, contractile tone increased by 122.4 +/- 12.9%, average. In group II contractile tone increased by mean 110%, time to pike decreased to 103 +/- 1.5 ms, while relaxation time--to 210.2 +/- 4.2 ms. Frequency of spontaneous stimulations as well as amplitude and duration of the action potential remained unchanged in all of the experiments. CONCLUSIONS: Positive chronotropic and inotropic action of histamine added to the extracellular fluid point to the presence of histaminergic receptor in rabbit's cardiac muscle. H2 histaminergic receptors are situated not only on the external surface of cellular membrane of rabbit's right heart atrium trabeculae, but also inside the cells. Experiments with histamine administration by the "cut end" method suggest that the role of intracellular H2 histaminergic receptors is associated with controlling the contractile processes of the cardiac muscle.

[Solitary extra-bone-marrow form of plasmacytoma: diagnostic difficulties]. / Odosobniona pozaszpikowa postac szpiczaka plazmocytowego--trudnosci diagnostyczne.

We present the patient with soft tissue tumor, which in histopathological examination proved to be plasmacytoma. Initial laboratory and radiological diagnostics did not suggest recognition.

[Invasive treatment of recent myocardial infarction. Evaluation of left ventricular function]. / Leczenie inwazyjne swiezego zawalu serca. Ocena funkcji lewej komory.

Hemodynamic parameters of left ventricular function were assessed in 179 patients with acute myocardial infarction, who were treated with intracoronary thrombolysis during first six hours after the onset of chest pain. Some of them were subjected to coronary angioplasty. Patency of the infarct related artery was controlled between the 2nd and 3rd week after acute myocardial infarction concomitant with evaluation of EF and LVEDP. Reperfusion of the infarct related artery was obtained in 121 patients (67.6%) and also significant increase of EF was observed in those patients. EF rose in patients with a patent coronary artery after 2-3 weeks (not significant) in contrast to patients with obstructed coronary artery in whom there was a fall in EF. The rise of EF was more pronounced in patients with reperfusion reached in 3 hours after the onset of infarct pain and without coronary angioplasty. It was shown that LVEDP is not usefull in estimation of left ventricular function.

[Complex ventricular arrhythmias in ischemic heart disease]. / Zlozone arytmie komorowe w chorobie niedokrwiennej serca.

The purpose of the study was to describe the clinical picture in patients with ischemic heart disease (IHD) and verifying severity of ventricular arrhythmias. The study included 856 patients with IHD aged 23-88 years (mean = 55.3), including 659 men and 197 women. Holter monitoring was performed in all patients. Ventricular arrhythmias were graded according to Lown. The patients were divided into five groups: group 1-349 patients with Lown's grade 1 and 2; group 2-95 patients with grade 3; group 3-152 patients with grade 4a and 4b; group 4-11 patients with grade 5; group 5-507 patients (selected from groups 2, 3 and 4) with Lown's grade 3 and 4 or 5. Arterial hypertension was found in 17.1%, myocardial infraction in 66%, and syncope in 12.3% of the patients. The patients with complex ventricular arrhythmias versus Lown's grade 1 and 2 show significant differences especially in respect to: the frequency of previous anterior myocardial infraction, the incidence of pain at rest, loss consciousness, the frequency of ventricular tachycardia and fibrillation, anginal pain and exercise-related arrhythmias. The patients with Lown's ventricular arrhythmia grade 3-5 do not differ significantly in their clinical manifestations of IHD from the patients with ventricular arrhythmias grade from 3 to 5. The development of silent myocardial ischemia during exercise stress testing is typical also for the patients with complex ventricular arrhythmias. A decreased contractility index, ejection fraction and dyskinesis are significantly more frequent in the patients with complex ventricular arrhythmias.

[Late right and left ventricular potentials using inter-cardiac recording in patients with ischemic heart disease--methodologic and clinical problems]. / Opóznione potencjaly prawo- i lewokomorowe rejestrowane z wnetrza serca u chorych z choroba niedokrwienna serca--problemy metodologiczne i kliniczne.

The aim of the study was to compare detection frequency of late inter-cardiac potentials recorded from the right and left ventricle. There was also estimated relationship between their incidence and ventricular tachycardia or fibrillation occurrence. 41 patients with ischemic heart disease underwent the study. Electrophysiologic examination were performed because of ventricular tachycardia and/or fibrillation attacks or complex ventricular arrhythmias recorded in ECG Holter monitoring. In 11 patients intracardiac electrocardiograms were recorded from both ventricles, in 29 only from the right and in 1 from the left one. All patients underwent programmed right and/or left ventricular stimulation. Left ventricular end-diastolic diameter, segmental contractility and ejection fraction were echocardiographically estimated. Study results were statistically analyzed by means of CHI2 and t-Student tests for unpaired variables. Late potentials were more frequently observed in patients with left ventricular dyskinesis (p less than 0.01) and decreased ejection fraction. Late potentials recorded in patients with a history of ventricular tachycardia or fibrillation were more delayed to proceeded QRS complex and had a greater amplitude. This prolongation of ventricular activation can make an anatomic substrate for dangerous ventricular arrhythmias occurrence. Since the presence of late potentials in patients with contractility disorders is connected with more frequent incidence of spontaneous and provoked ventricular arrhythmias, endocardial late potentials recording may be of a prognostic value, if it is performed from both ventricles.

[Comparative evaluation of the results of Holter monitoring and programmed ventricular stimulation in patients with ischemic heart disease]. / Ocena porównawcza wyników badania holterowskiego i programowanej stymulacji komór u osób z choroba niedokrwienna serca.

24-hour ECG Holter monitoring and programmed ventricular stimulation were performed in 81 patients (64 males and 17 females aged 35-65). No ++anti-arrhythythmic agents nor beta-blockers were administrated. 58 patients suffered from myocardial infarction in the past, and 38 had a history of ventricular tachycardia. Right atrial and ventricular stimulation (in 7 patients also left ventricular stimulation) was performed using stimuli of a 2 ms pulse width. 24-hour ECG Holter monitoring was recorded on a magnetic tape from two bipolar precordial leads. Both examinations results were compared to assess correlation between ECG Holter monitoring parameters and inducibility of VT or VF by programmed stimulation. Significant correlation was stated among occurrence of: 1) spontaneous sustained ventricular tachycardia and induced by stimulation monomorphic sustained VT (p less than 0.005) as well as estimated both sustained and nonsustained VT (p less than 0.010) 2) spontaneous nonsustained VT and induced by stimulation sustained or nonsustained monomorphic VT (p less than 0.025). There was no correlation between spontaneous ventricular arrhythmias estimated by Lown and Wolf's classification and possibility to induce monomorphic VT as well as between any of ECG Holter monitoring parameters and polymorphic VT or ventricular fibrillation induced by stimulation. Aggressiveness extent of stimulation protocol necessary to induce monomorphic VT was similar in patients with or without VT recorded by Holter method.

[Ventricular arrhythmias and QT/QS2 index in patients with ischemic heart disease]. / Arytmie komorowe, a wskaznik QT/QS2 u chorych z choroba niedokrwienna serca.

This multicenter study comprised a group of 900 patients (207 females and 693 males, aged 23-68 years, mean 53) with ischaemic heart disease. Go medications other than nitrates, nifedipine and diuretics were administered at the time of study. In all patients a simultaneous standard 12-lead ecg and a phonocardiogram was registered. QT and QS2 intervals were then measured, and the QT/QS2 index calculated. QT/QS2 ratio 1.0 was considered as a normal one. A 24-h Holter ecg monitoring was performed in each patients, and ectopic ventricular activity was graded according to the Lown's classification. For patients with each class of arrhythmia the mean value of QT/QS2 was calculated. All means were similar, with values 1.0. Proportion of patients with abnormal values of QT/QS2 index was similar in patients showing different Lown classes of arrhythmia. Since a 24-hour monitoring does not give a full information about the arrhythmic events, patients with the history of VT/VF were analyzed separately. In this group an increase of QT/QS2 index was observed significantly more frequently than in other patients (37% vs 19%, p = 0.016). It is concluded that no close relationship exists between QT/QS2 index and the type of ventricular arrhythmia found on the Holter monitoring. However, pathologic QT/QS2 values seem to characterize the patients with increase risk of VT/VF.

[Programmed electrical stimulation of the heart in relation to left ventricular contractility in ischemic heart disease]. / Programowana stymulacja elektryczna serca a kurczliwosc lewej komory w chorobie niedokrwiennej.

To determine the relation between left ventricular contractility disorders and the inducibility of serious ventricular arrhythmias, 83 patients (pts) with ischaemic heart disease and ventricular tachycardia (VT) or fibrillation (VF) in history and/or Lown's class IVb arrhythmia in 24-hour Holter ECG monitoring were evaluated by means of echocardiography and programmed electrical stimulation (PES) of the heart. Inducible VT or VF were observed in 66% of pts: sustained monomorphic VT (SMVT) in 33%, nonsustained VT (NSVT) in 28% and VF in 6%. VT or VF were significantly more frequent in patients with VT/VF in history (91% vs 42%, p less than 0.001), SMVT (48% vs 17%, p less than 0.01) as well as NSVT (38% vs 17%, p less than 0.01). Low ejection fraction (EF less than 40%) was observed in 18 pts (22%), VT/VF was inducible in 94% of them, while only in 57% with EF greater than or equal to 40%, p less than 0.01, SMVT in 39% vs 30%, NSVT in 33% vs 25%. Among 21 pts (21%) with left ventricular (LV) dyskinesis in 91% of pts while only in 55% without it, p less than 0.01, SMVT in 53% vs 26%, p less than 0.05. We concluded that in patients with previous myocardial infarction, VT/VF in history and abnormal LV contractility full haemodynamic, angiographic and electrophysiologic examination should be performed to determine their risk of sudden death due to serious ventricular arrhythmia before final decision about the mode of treatment.

Mechanism of intercellular synchronization in the rabbit sinus node.

A strip of tissue cut from the sinus node, 0.5 mm wide, was studied in a sucrose gap chamber. With the gap width of 0.6--1.5 mm the 2 ends of the preparation showed nonsynchronous activity. Synchronization could be re-established by a shunt resistor, 15--100 k omega, connected across the gap, suggesting that synchronous firing of the sinus node requires local circuit currents.

Do the intracellular beta adrenoreceptors exist in the rabbit auricle.

Propranolol introduced by a cut-end method into atrial trabeculae evoked negative inotropic response without any significant changes in basic electrical parameters. This effect was resistant to noradrenaline but not to dibutyryl cAMP. These results suggest that existence of intracellular beta adrenoreceptors involved in the control of the contraction.

The effect of cGMP in rabbit auricle as studied by a cut-end method.

Cyclic GMP was applied to the rabbit right auricle by a cut-end method. The nucleotide decreased the spontaneous rate, hyperpolarized the cell membrane and reduced the amplitude and the slow component of the action potential. It also decreased the force of contraction. These results suggest that cGMP may be the mediator of the action of acetylcholine in the rabbit auricle.

Effect of exogenous cAMP in the rabbit right auricle.

Isotonic solution of cAMP-Na was applied into spontaneously beating auricular fibres by a cut-end method. Cyclic AMP enhanced the spontaneous rate (mean 48%) and increased the contractile tension (mean 297%). These results provided direct evidence that cAMP is involved in the spontaneous activity and contraction in the heart muscle.

The influence of dibutyryl cGMP on the rabbit auricle.

Dibutyryl cGMP, like acetylcholine, shortens and reduces repolarization and overshoot of the action potential, slightly hyperpolarizes the cell and decreases the force of the contraction in the atrial working muscle. It suggests that cGMP may mediate the action of acetylcholine in the atrial working fibres.

Inotropic effect of noradrenaline and acetylcholine in the rabbit auricle studied by a cut-end method.

Trans-gap application of noradrenaline or acetylcholine evoked pronounced inotropic but no chronotropic effects in spontaneously active rabbit auricle preparations. These results suggest the existence of intracellular receptors, both adrenergic and cholinergic, which were involved in the control of auricular contraction.

Iontrophoretic application of autonomic mediators and cyclic nucleotides in the sinus node cells.

The effects of intracellular application of noradrenaline, acetylcholine, cAMP and cGMP were studied in the sinus-node of the rabbit. Noradrenaline and acetylcholine were without effect on electrical activity. In about one third of cases, cAMP increased, and cGMP decreased the slope of slow depolarization. These results suggest that adrenergic as well as cholinergic receptors which control the electrical activity of the sinus node cell are localized at the outer side of the cell membrane. It has also been shown that the cyclic nucleotides exert direct but opposite chronotropic effects.