Atrial preparation

In the rat, we observed a decrease of the spontaneous frequency of right atrial preparations and biphasic inotropic effects in left atrial preparations. Negative effects were not antagonized by atropine. The positive inotropic effect was modified very little by prior reserpinization or prior exposure to propranolol and phentolamine but was sensitive to Mn ions. On the other hand. 

Other authors showed that (R)a-methylhistamine, together with the inotropic and chronotropic adrenergic response from transmurally-stimulated atrial preparations, also inhibits the release of noradrenaline, thus providing direct evidence that histamine H3-receptors negatively modulate the cardiac sympathetic activity at a presynaptic site of action (Endou et al., 1994). In addition, it was demonstrated that (R)a-methylhistamine, at concentrations greater than 1 pM, produces further antiadrenergic activity by acting at inhibitory presynaptic a.2-adrenoceptors. This result is supported by the fact that yohimbine reverses this effect. 

In wild-type atrial preparations, increasing concentrations of the nonselective a2-AR agonist UK-14,304 dose dependently inhibited electrically-stimulated [3H]norepinephrine release (21). Consistent with previous studies, a2A-AR ablation did not completely attenuate the effects of UK-14,304 in suppressing [3H]norepinephrine release. In contrast, atrial preparations derived from o ac-AR 7 mice were completely unresponsive to UK-14,304 in this functional assay. Additional studies revealed that the o a-AR and o c-AR subtypes serve distinct roles in the regulation of neurotransmitter release (Table 1). Frequency inhibition studies showed that the a2C-AR is fine-tuned to respond to low-frequency stimulation (i.e., low norepinephrine concentrations), whereas the o a-AR is geared to respond to high-frequency stimulation (i.e., high norepinephrine concentrations as would be elicited by sympathetic activation). 

The potential role of the calcium current in the genesis of arrhythmias was discussed above. Verapamil (M, which inhibits calcium influx, can suppress experimental arrhythmias30 Another calcium blocker, nifedipine ( 13a), inhibits irregular rhythms produced by calcium in isolated atrial preparations.31 The calcium antagonist TMB-6( lk) was reported to be as effective as lidocaine in suppressing digoxin-induced arrhythmias in dogs.32 As expected, inhibition of calcium influx leads to depression of cardiac contractility and atrioventricular conduction. 

Martin N, Bardisa L, Pantoja C, Vargas M, QiiezadaP, Valenzuela J (1994) Anti-arrhytlimic profile of a garlic dialysale assayed in dogs and isolated atrial preparations. J Ethnopharmacol 43(l) l-8. doi 10.1016/0378-8741(94)90109-0... 

Activation Atrial preparation Biophysics Calcium channel Cardiac action potential Channel kinetics Comprehensive in vitro proarrhythmia assay Delayed rectifier Early afterdepolarisation ECG Hodgkin-Huxley ICHS7A ICHS7B In silico modelling Inactivation Inward rectifier Langendorff heart Purkinje fibre Safety assessment Sodium channel Stem cells... 

We have been using and Cl liquid ion exchanger microelectrodes to measure intracellular activities of K+ and Cl in frog heart. In these studies we have used three kinds of heart muscle ventricle, atrium and sinus venosus. The preparations are small pieces of tissue cut from the heart and pinned down in a chamber where they are superfused with frog Ringers solution. The ventricular and atrial preparations are quiescent unless stimulated in these experiments they are driven at a frequency of 0.5 stimuli/sec. The sinus venosus preparations are spontaneously active. 

Dantrolene is the mainstay of MH treatment. It has long been available for the treatment of muscle spasm in cerebral palsy and similar diseases. It is a hydantoin derivative that was first synthesized in 1967, and reported to be effective in the treatment of porcine MH in 1975. Also in 1975, dantrolene was shown to be more effective than procainamide in the treatment of human MH, which until that time was the drug of choice. However, the intravenous preparation was not made available until November 1979. It significantly lowered mortality. The half-life of dantrolene is estimated to be 6-8 hr. Dantrolene s primary mode of action is the reduction in calcium release by the sarcoplasmic reticulum. Dantrolene also exerts a primary antiarrhythmic effect by increasing atrial and ventricular refractory periods. Side effects of dentrolene include hepatotoxicity, muscle weakness, ataxia, blurred vision, slurred speech, nausea, and vomiting. Dantrolene is not contraindicated in pregnancy, but it does cross into breast milk and its effect on the neonate is unknown. 

Cochlearenine (11) was tested on isolated heart preparations and caused a dose-dependent (0.3-3.0 mg/ml) fall in heart rate, while a mild increase in the atrial force... 

The most recent reports on the action of the water soluble toxin from G, toxicus concluded that this toxin, referred to as maitotoxin, invokes an unmediated stimulatory (contractile) response on contact with guinea pig ileal smooth muscle preparations. Furthermore, this response was said to be due to an activation of calcium channels in the smooth muscle membranes (J7). Previous studies of this toxin from the same source indicated that it produces an inhibitory effect on guinea pig atrial muscle (28, 19). 

Atrial flutter or fibrillation Reversion to sinus rhythm may be preceded by a progressive reduction in degree of AV block to a 1 1 ratio, which results in an extremely rapid ventricular rate. Prior to use in atrial flutter, pretreat with digitalis preparation. 

Ipecac syrup is prepared from the dried rhizome and roots of Cephaelis ipecacuanha or Cephaelis acuminata, plants from Brazil and Central America that have the alkaloid emetine as their active principal ingredient. It acts directly on the CTZ and also indirectly by irritating the gastric mucosa. Ipecac is cardiotoxic if absorbed and can cause cardiac conduction disturbances, atrial fibrillation, or fatal myocarditis. If emesis does not occur, gastric lavage using a nasogastric tube must be performed. 

Recently, both hirsutine (85) and dihydrocorynantheine (86) were found to be active when the effects of these compounds on the action potentials of sino-atrial node, atrium and ventricle tissues were studied with standard microelectrode techniques [65]. In sino-atrial node preparations, both compounds concentration-dependently increased cycle length, decreased the slope of the pacemaker depolarization, decreased the maximum rate of rise and prolonged action potential duration. Thus, it was for the first time shown that hirsutine and dihydrocorynantheine have direct inhibitory effects on the cardiac pacemaker. In atrial and ventricular preparations, both compounds concentration-dependently decreased the maximum rate of rise and prolonged action potential duration. Although stereochemically different, these two alkaloids exhibited no difference in their effects on various myocardial action potential parameters. Dihydrocorynantheine also displays potent a-adrenoceptor blocking activity, while hirsutine is inactive [66]. Experiments with ion channels indicate that the mechanisms for these two phenomena probably differ. The direct effects of hirsutine and dihydrocorynantheine on the action potential of cardiac muscle through inhibition of multiple ion channels may explain the negative chronotropic and antiarrhythmic activities of these two alkaloids. 

In 1983 de Bold et al. 202) first isolated an atrial peptide ANP-(6-33) from homogenates of rat atrial muscle and elucidated its structure (Fig. 14). In January 1984, K. Kangawa et al. prepared pure samples of the a-human atrial natriuretic peptide a-h-ANP-(6-33 Met17) 203) and of the hitherto longest-known natriuretic peptide containing 126 amino acids, y-h-ANP 204), from human atrial tissue. 

In a subsequent investigation by the author (3) arylated furan- and thiophenecarbox-amides, (III), were prepared and were effective in the treatment of atrial fibrillation or atrial flutters. 

Ultrarapidly activating potassium Kvl.5 channel blockers consisting of benzamide derivatives, (II), prepared by Baker (4) were effective in treating atrial fibrillation disorders. 

Aminocycloalkyl cinnamide derivatives, (III), prepared by Beatch (3) were effective in the treatment and termination of atrial fibrillation/flutter arrhythmia events. 

Pumiliotoxin B has both cardiotonic and myotonic activity in isolated atrial or rat phrenic nerve diaphragm preparations (97). The cardiotonic activity is markedly dependent on the structure of the pumiliotoxin (95). Subsequent studies on the activity of pumiliotoxin B in neuromuscular preparations were interpreted as due to an apparent facilitation of calcium translocation from internal storage sites (99 see review in Ref. 5). Inhibitory effects on the calcium-dependent ATPase of sarcoplasmic reticulum were shown to be due not to pumiliotoxin B, but to phenolic impurities, namely, fcis(2-hydroxy-3-terf-butyl-5-methylphenyl)methane, 3,5-di-/ert-butyl-4-hydroxytoluene (BHT), and nonylphenols (100). 

Shuayb, W. A., Moran, W. H., Jr., and Zimmermann, B., Hypersecretion of antidiuretic hormone following release of left atrial distension. In preparation (1972). 

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