Effect of D600, practolol, and alterations in magnesium on ionized calcium concentration-response relationships in the intact dog heart.

Bristow, Michael R.; Daniels, John R.; Kernoff, Robert S.; Harrison, Donald C.

doi:10.1161/01.res.41.4.574

Cited by 14 publications

(6 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…20 This is shown by the effect of the ^-blocking agent practolol on the ionized calcium-dP/dt relationship. 21 The quantitative effects of Ca 2+ on electrical measurements that reflect the plateau phase of the action potential are also precise and repeatable. The electrical interval S a T c was the easiest to measure and correlated best with Ca 2+ in all ranges that are likely to be encountered clinically (Ca 2+ of 1-3, 3-6, 6-10 mg/100 ml).…”

Section: Camentioning

confidence: 99%

“…Support for a reduction of ionized magnesium as the mediator of this effect is given in a companion publication. 21 Although it is difficult to extrapolate from animal studies, the ease and speed with which one is able to alter Ca 2+ with sodium citrate and the resultant control that one has over Ca 2+ concentration-response relationships suggest that citrate infusions monitored by frequent Ca 2+ measurements would be an ideal acute treatment in hypercalcemia, for which there is a paucity of safe measures that can quickly lower plasma Ca 2+ . 24 If the infusion were continued for several hours, the large sodium load in Na 3 citrate would probably cause metabolic alkalosis (not seen in this study) and would have to be dealt with.…”

Section: Camentioning

confidence: 99%

See 1 more Smart Citation

Ionized calcium and the heart. Elucidation of in vivo concentration-response relationships in the open-chest dog.

Bristow¹,

Schwartz²,

Binetti³

et al. 1977

Circ Res

Self Cite

View full text Add to dashboard Cite

SUMMARY Pharmacological relationships between ionized calcium and cardiac electric and mechanical parameters were explored in the open-chest dog. A technique that allows the determination of reliable, repeatable concentration-response relationships in vivo was developed. This method consists of alternating infusions of sodium citrate and calcium gluconate and direct measurement of serum ionized calcium by an ion-specific electrode. With this technique, four consecutive curves for ionized calcium vs. the first derivative of the left ventricular pressure (dP/dt) were essentially superimposable within the limits of 2-10 mg/100 ml. Relationships between ionized calcium and the electrocardiograph (ECG) interval measured from the end of the S wave to the peak of the T wave (S a T c ) proved to be superior to other ECG measurements as a correlate of ionized calcium. Ionized calcium correlated better than total calcium with physiological function in several situations. Postsurgical ionized calcium levels (4.92 ± 0.10 mg/100 ml) were consistently higher than preanesthetic values (4.57 ± 0.07 mg/100 ml, P < 0.025), whereas total calcium measurements were not significantly different (X = 5.3 ± 0.10 mEq/liter, X = 5.1 ± 0.10 mEq/liter, P < 0.1). This difference in ionized calcium was shown to be able to account for significant alterations in dP/dt, suggesting that fluctuations in ionized calcium may be involved in the regulation of the contractile state of the heart. VARIATIONS in the extracellular concentration of ionized calcium (Ca 2+ ) have important effects on the electrical and mechanical function of the intact mammalian heart. In man, hypocalcemia associated with rapid transfusion of citrated blood has been implicated as a cause of decreased contractility, cardiovascular collapse, and cardiac arrest.1 " 4 Hypercalcemia has been associated with an increase in contractility in animals, 5 " 7 and conduction disturbances, ventricular irritability, and cardiac arrest have been.described in man. 8 " 10 Recent studies have shown that the fraction of myocardial calcium that is correlated with contractility is readily exchangeable and in rapid equilibrium with plasma Ca 2 " 1 ". 11- 12 Since it has been suggested that alterations in cellular calcium levels are a common mediator of a variety of pharmacological influences on the contractile state of the heart, 13 it is possible that minor as well as major changes in the extracellular Ca 2+ can have important effects on cardiac function.Because to determine quantitative relationships in vivo between Ca 2+ and myocardial response throughout a wide range of serum Ca 2+ . MethodsTwenty-two mongrel dogs weighing 14-30 kg were sedated with morphine sulfate (2 mg/kg) intramuscularly, then anesthetized with intravenous chloralose and urethane at doses of 85 mg/kg and 625 mg/kg, respectively. Ventilation was provided by a Harvard pump delivering room air through a cuffed endotracheal tube. Arterial blood gases were monitored frequently with a Corning model 165 gas analyzer and pH w...

show abstract

Section: Camentioning

confidence: 99%

Section: Camentioning

confidence: 99%

Ionized calcium and the heart. Elucidation of in vivo concentration-response relationships in the open-chest dog.

Bristow¹,

Schwartz²,

Binetti³

et al. 1977

Circ Res

Self Cite

View full text Add to dashboard Cite

show abstract

“…The time between vessel occlusion and the development of VF-the VF latencycan be measured repeatedly before and after experimental interventions. Since the model involves the production of global left ventricular ischemia, changes in the time course of arrhythmia development can be correlated with simultaneous measurements of coronary blood flow and left ventricular work.In the present study we have compared the effects of the calcium influx blocker diltiazem with reduction of serum ionized calcium by infusion of sodium citrate (Bristow et al, 1977a(Bristow et al, , 1977b. We find that both of these treatments invariably produce a concentration-dependent increase in the latency of VF compared with the control trials.…”

mentioning

confidence: 83%

“…In the present study we have compared the effects of the calcium influx blocker diltiazem with reduction of serum ionized calcium by infusion of sodium citrate (Bristow et al, 1977a(Bristow et al, , 1977b. We find that both of these treatments invariably produce a concentration-dependent increase in the latency of VF compared with the control trials.…”

mentioning

confidence: 83%

The effects of diltiazem and reduced serum ionized calcium on ischemic ventricular fibrillation in the dog.

Clusin¹,

Bristow²,

Baim³

et al. 1982

Circ Res

Self Cite

View full text Add to dashboard Cite

SUMMARY. Calcium influx blockers reportedly suppress ventricular arrhythmias during acute ischemia. We therefore studied the effects of diltiazem and reduced serum ionized calcium on ventricular fibrillation (VF) in a reversible ligation model. VF was produced at 15-minute intervals by simultaneous occlusion of the left anterior descending and circumflex arteries of 31 dogs. Time from coronary occlusion to onset of VF showed no significant variation during 15 consecutive trials in six dogs that received saline alone. Intravenous infusion of diltiazem (0.02 mg/kg per min) markedly delayed the onset of VF in each of 10 dogs (P < 0.0001). Mean VF latency increased from 138 to 295 seconds during a 45-minute diltiazem infusion, declined exponentially when the infusion ceased, and was strongly correlated with serum diltiazem concentration (r = 0.96, P < 10~6). In five dogs, hemodynamic measurements, including coronary venous blood flow, were performed during each occlusion. The increase in VF latency by diltiazem was not due to increased coronary flow during occlusion or to reduction of left ventricular (LV) mechanical work. In six dogs, mean serum ionized calcium, [Ca ++ ], was reduced from 1.11 to 0.59 mM by infusion of sodium citrate. Citrate infusion increased mean VF latency from 155 to 243 seconds, and the increase observed in each dog was correlated (r = 0.84, P < 10~6) with the reduction in [Ca ++ ], VF latency was unaffected by lidocaine in nine dogs. The antifibrillatory effect of diltiazem during global LV ischemia may be an electrophysiological phenomenon related to reduction of cellular calcium influx. (Circ Res 50: 518-526, 1982) MORE than 10 years ago, Kaumann and Aramendia (1968) reported that the calcium influx blocker, verapamil, produces a dramatic reduction in the incidence of ventricular fibrillation following coronary artery ligation. This finding has been corroborated in several subsequent studies (Kaumann and Serur, 1975;Fondacaro et al., 1978, Brooks et al., 1980, but its physiological basis remains obscure. Calcium influx blockers are thought to improve myocardial metabolism during ischemia by alleviating intracellular calcium overload (Katz and Reuter, 1979), and they also suppress transmembrane currents that may mediate certain arrhythmias (Cranefield, 1975(Cranefield, , 1977. Furthermore, since calcium influx blockers are potent coronary vasodilators, they might prevent fibrillation by improving the distribution of coronary blood flow.The risk of VF following permanent coronary ligation is difficult to measure precisely in a manageable number of experimental animals. We have therefore developed a reversible ligation model in which the degree of ischemia is severe enough that VF occurs swiftly and predictably during successive trials (Clusin et al., 1979. The time between vessel occlusion and the development of VF-the VF latencycan be measured repeatedly before and after experimental interventions. Since the model involves the production of global left ventricular ischemia, changes...

show abstract

“…Magnesium displaces extracellular Ca 2÷ from its normal low-affinity binding sites in the glycocalyx, especially in the rat heart, and consequently myocardial tension development is reduced [13,15]. There is a Ca2+-Mg 2+ antagonism on contractility in rat ventricular muscle [15,31] and in the dog heart in situ [32]. In isolated myocardial fibers, decreasing external Mg 2+ concentration augments tension development by allowing more Ca 2÷ ions to interact with troponin [33].…”

Section: Mechanism Of Antiarrhythmic Effect Of Magnesiummentioning

confidence: 99%

Effects of magnesium on ischemic and reperfusion arrhythmias in the rat heart and electrophysiologic effects of hypermagnesemia in the anesthetized dog

Keren

Dorian

Davy

et al. 1988

Cardiovasc Drug Ther

View full text Add to dashboard Cite

Magnesium sulfate, reportedly clinically effective against some ventricular arrhythmias, has not been extensively studied for its effects on experimental ischemic and reperfusion arrhythmias. We evaluated the effects of three high extracellular concentrations of magnesium (Mg2+) 1.19, 2.38, and 4.76 mM in 70 isolated perfused rat hearts following coronary artery ligation and reperfusion, at each of three different perfusate ionized calcium (Ca2+) concentrations (0.9, 1.25, and, 2.5 mM), where 1.25 mM is close to physiologic. At 0.9 mM Ca2+, higher concentrations of Mg2+ increased the sinus node cycle length (p less than 0.02) and virtually abolished ischemic ventricular tachycardia (VT) and reperfusion ventricular fibrillation (VF) (p less than 0.01), otherwise consistently found in this model. At 1.25 and 2.5 mM Ca2+ increasing Mg2+ had no effect on the incidence of ischemic or reperfusion arrhythmias, although at 1.25 mM Ca2+ ischemic VT had longer cycle lengths and VT appeared after a longer delay (p less than 0.01). In the nonischemic dog heart, marked increases of serum Mg2+ progressively prolonged the A-H, H-V, and QR S intervals, the ventricular effective refractory period, and the sinus cycle length, while the arterial blood pressure fell. Because of its relatively modest electrophysiologic and hemodynamic effects, it is inferred that intravenous magnesium may be given therapeutically with relative safety.

show abstract

Effect of D600, practolol, and alterations in magnesium on ionized calcium concentration-response relationships in the intact dog heart.

Cited by 14 publications

References 16 publications

Ionized calcium and the heart. Elucidation of in vivo concentration-response relationships in the open-chest dog.

Ionized calcium and the heart. Elucidation of in vivo concentration-response relationships in the open-chest dog.

The effects of diltiazem and reduced serum ionized calcium on ischemic ventricular fibrillation in the dog.

Effects of magnesium on ischemic and reperfusion arrhythmias in the rat heart and electrophysiologic effects of hypermagnesemia in the anesthetized dog

Contact Info

Product

Resources

About