The Influence of Ketamine on Inotropic and Chronotropic Responsiveness of Heart Muscle

Adams, H. R.; Parker, J. L.; Mathew, Bobby

doi:10.1097/00132586-197802000-00025

Cited by 15 publications

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“…The results of the present study show that in rat isolated atria ketamine decreased atrial rate in a dose-dependent manner similar to that previously observed in isolated preparations of other species (Dowdy & Kaya, 1968;Traber, Wilson & Priano, 1968;Goldberg et al, 1970;Adams et al, 1977). Paradoxically, and in contrast to previous reports, ketamine in either spontaneously beating right atria or in electrically driven left atria produced a dose- dependent increase in peak contractile force.…”

Section: Ketamine Interaction With Reserpine Practolol and Isoprenalinesupporting

confidence: 90%

“…For example, the cardioexcitatory effects of ketamine have been ascribed to: release of catecholamines from peripheral tissue stores (Virtue, Alanis, Mori, Lafargue, Vogel & Metcalf, 1967), a cocaine-like effect (Nedergaard, 1973), stimulation of central cardiovascular mechanisms resulting in increased sympathetic efferent discharge (McCarthy et al, 1965;Traber & Wilson, 1969), diminution of frequency response of the carotid sinus baroreceptors (Dowdy & Kaya, 1968), inhibition of the vagal component of the baroreceptor reflex (McGrath, MacKenzie & Millar, 1975) and release of renal renin (Tanaka & Pettinger, 1974). Ketamine has also been shown to produce dose-dependent negative chronotropic and inotropic effects in rabbit isolated per-0007-1188/82/050085-09 $01.00 fused heart (Dowdy & Kaya, 1968), in left ventricular trabeculae cameae of the rat (Goldberg, Keane & Phear, 1970), in dog ventricle (Schwartz & Horwitz, 1975) and in guinea-pig atria (Adams, Parker & Mathew, 1977). The consensus, therefore, is that ketamine increases cardiac function by modifying autonomic nervous system discharge (Goldberg et al, 1970;Schwartz & Horwirtz, 1975).…”

Section: Introductionmentioning

confidence: 99%

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The Mechanism of the Positive Inotropic Action of Ketamine on Isolated Atria of the Rat

Barrigón

Miguel

Tamargo

et al. 1982

British J Pharmacology

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1 The effect of ketamine (10-7 M-5 x 10-4 M) on electrical and mechanical properties of isolated atria of the rat was investigated. 2 On spontaneously beating right atria, ketamine produced a dose-dependent positive inotropic effect which was accompanied by a progressive reduction in atrial rate. 3 In electrically driven left atria, ketamine produced a dose-dependent positive inotropic effect which was accompanied by a parallel increase in df/dtm,, and by a prolongation in the time to peak tension and in the time for total contraction. The positive inotropic effect occurred concomitantly with an increase in the height and duration of the plateau phase of the action potential of atrial fibres. 4 The positive inotropic effect of ketamine varied with the concentration of Ca and Na in the bathing media and the rate of stimulation. 5 Ketamine decreased post-extrasystolic potentiation and the amplitude-interval relationship. 6 The positive inotropic effect of ketamine was inhibited by verapamil (10-6 M) and by caffeine (4x 103 M).7 Ketamine, 5 x 10-5 M and 10-4 M, increased 45Ca uptake in electrically driven left atria. At 10-4 M and 5 x 10-4 M, ketamine also increased 45Ca efflux. 8 These results suggest that ketamine produces its positive inotropic effect by two possible mechanisms. One of these is presumed to be an effect on the cell membrane which leads to an increased Ca influx into atrial fibres; the other is probably related to the inhibition of Ca sequestration by the sarcoplasmic reticulum.

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Section: Ketamine Interaction With Reserpine Practolol and Isoprenalinesupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

The Mechanism of the Positive Inotropic Action of Ketamine on Isolated Atria of the Rat

Barrigón

Miguel

Tamargo

et al. 1982

British J Pharmacology

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“…Present findings indicate that the cardiac depressant effects of gentamicin, a representative aminoglycoside antibiotic, are profoundly augmented in myocardium contracting under "slow Ca++-activated" conditions. METHODS Left atria of male albino guinea pigs were prepared for monitoring isometric contractile tension and its first derivative (dTldt) according to a method previously reported in detail (15). Electrical stimulation of the atria with single square wave impulses was accomplished with an AEL stimulator (American Electronic Laboratories, Colmar, Pa.) and a miniature bipolar electrode.…”

Section: Introductionmentioning

confidence: 99%

Gentamicin blockade of slow Ca++ channels in atrial myocardium of guinea pigs.

Adams¹,

Durrett²

1978

J. Clin. Invest.

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“…The tight-seal, whole cell voltage clamp technique was used. After the gigaohmseal between the tip of the electrode and the cell membrane was established, the membrane patch was disrupted by Ketamine affects the contractile tension and the action potential configuration in isolated mammalian myocardial preparations [1,2,24]. It has been demonstrated that ketamine inhibits several potassium currents and L-type calcium current (I Ca ) in isolated single cardiomyocytes of guinea pigs and rats [6].…”

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confidence: 99%

Tonic Block of the Sodium and Calcium Currents by Ketamine in Isolated Guinea Pig Ventricular Myocytes.

Hara

Chugun

Nakaya

et al. 1998

The Journal of Veterinary Medical Science

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ABSTRACT. Effects of ketamine on the sodium (I Na ) and L-type calcium currents (I Ca ) were examined by using whole-cell patch clamp techniques in guinea pig single ventricular myocytes. The mode of action of ketamine was compared with those of quinidine, a sodium channel blocker, and verapamil, a calcium channel blocker. Ketamine (30-300 µM) inhibited both I Na and I Ca in a concentrationdependent manner. Quinidine (30 µM) and verapamil (0.1 µM) produced use-dependent depression of I Na and I Ca , respectively. The amplitude of I Na elicited by the first depolarizing pulse after a long quiescent period was slightly decreased by quinidine. During a train of depolarizing pulse the current amplitude decreased gradually, and reached a steady state level in the quinidine-treated cells (use-dependent block, UDB). Verapamil produced a similar mode of inhibition of I Ca , i.e., UDB. In contrast, ketamine produced significant decrease in I Na and I Ca elicited by the first depolarizing pulses and the decreases of both currents were not augmented during a train of depolarizing pulses. From these results, it can be concluded that ketamine produces tonic block of the cardiac sodium and calcium channels and the mode of inhibition is clearly different from UDB by quinidine and verapamil. -KEY WORDS: calcium current, cardiac myocyte, ketamine, sodium current, tonic block.J. Vet. Med. Sci. 60(4): 479-483, 1998 MATERIALS AND METHODSCell preparations: Guinea pigs, weighing 200-350 g, were used in this study. Single ventricular cells were isolated by an enzymatic dispersion, as previously described [11]. Briefly, the heart was removed from the open-chest guinea pig anesthetized with pentobarbital Na, and mounted on a modified Langendorff perfusion system for retrograde perfusion of the coronary circulation with a normal HEPESTyrode solution. The perfusion medium was then changed to a nominally Ca-free HEPES-Tyrode solution and then to a solution containing 0.02% w/v collagenase (Wako, Osaka, Japan). After digestion, the heart was perfused with a high K + and low Cl -solution (modified Kraftbrühe (KB) solution) [17,22]. Ventricular tissue was cut into small pieces in the modified KB solution and gently shaken to isolate cells. Dispersed cells were stored in the KB solution at 4°C and used over the next 7-10 hr.Recording techniques: Whole-cell membrane currents were recorded by patch clamp method [9]. Single ventricular cells were placed in a recording chamber (1-ml volume) attached to an inverted microscope (Olympus IMT-2, Tokyo, Japan) and superfused with the HEPES-Tyrode solution at a rate of 3 ml/min. The temperature of the external solution was kept constant at 36 ± 1°C. Glass patch pipettes with a diameter of 1.5 mm were filled with a pipette solution. The resistance of the patch pipette filled with the pipette solution was 2-3 MΩ. The tight-seal, whole cell voltage clamp technique was used. After the gigaohmseal between the tip of the electrode and the cell membrane was established, the membrane patch was disrupted by K...

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The Influence of Ketamine on Inotropic and Chronotropic Responsiveness of Heart Muscle

Cited by 15 publications

References 0 publications

The Mechanism of the Positive Inotropic Action of Ketamine on Isolated Atria of the Rat

The Mechanism of the Positive Inotropic Action of Ketamine on Isolated Atria of the Rat

Gentamicin blockade of slow Ca++ channels in atrial myocardium of guinea pigs.

Tonic Block of the Sodium and Calcium Currents by Ketamine in Isolated Guinea Pig Ventricular Myocytes.

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