Cardioactive Drugs Research Articles

Responses to cardioactive drugs of fetal mouse hearts maintained in organ culture.

Responses to cardioactive drugs of fetal mouse hearts maintained in organ culture.

The influence of some cardioactive drugs on the energy-dependent uptake of calcium, potassium and adenine nucleotides by mitochondria

A number of cardioactive substances were studied for their influence on isolated mitochondria obtained from rat liver and rabbit heart. Among several drugs tested, quinidine, dl-propranolol, l-alprenolol, dl-oxyfedrin and tetracaine appeared to be the most active in decreasing or blocking the rate of energy-dependent uptake of calcium, potassium and adenine nucleotides in an incubation medium containing substrate (succinate or glutamate/fumarate), MgCl 2, phosphate and approximately 5 mg of mitochondrial protein. The effective concentrations (5 × 10 −5 m to 10 −3 m) were comparable to those employed by other investigators to block the effects on the ATP-dependent calcium accumulation and the ATPase-activity of isolated sarcotubular fractions of heart and skeletal muscle by means of quinidine and propranolol. It is concluded that the rate-inhibiting effects of the active drugs on the velocity and the extent of calcium, potassium, and adenine nucleotide uptake could determine their effect on cardiac contractility.

The Actions of Cardioactive Drugs on Developing Myocardium

Clinicians have long recognized age related differences in cardiac pharmacology. These phenomena may reflect altered drug metabolism or disposition in the immature organism and/or an altered sensitivity of fetal and neonatal myocardium per se. The latter possibility was examined by studying the responsiveness to cardioactive drugs of heart muscle isolated from a total of 100 fetal, newborn, and adult sheep and swine. The enhancement of cardiac contractility produced by digitalis was significantly greater in newborn than adult heart. However, newborn myocardium required significantly more digitalis to achieve a peal inotropic effect or to demonstrate evidence of toxicity when compared to the adult. Fetal and adult cardiac muscle was equally responsive to isoproterenol, and acetylcholine. Fetal heart was supersensitive to the positive inotropic effects of norepinephrine. At all ages acidosis attenuated the augmentation of contractility produced by norepinephrine. Propranolol exerted a morc profound negative inotropic action on fetal than adult heart, although the effectiveness of beta adrenergic receptor blockade by propranolol was equal in fetal and adult myocardium. Glucagon exerted a negative inotropic effect on fetal cardiac muscle, a small positive inotropic effect in newborns, and a marked augmentation of contractility in the adult. Thus, a marked agedependency of the myocardial resonses to many cardioactive drugs exists that must be considered in any clinical evaluation of cardiac pharmacology in the perinatal period.

The influence of propranolol, inpea, iproveratril and some 1-naphthylethylamine derivatives on the myocardial phosphorylase activity

The antiarrhythmic or negative inotropic and chronotropic response to drugs may be the result of β-adrenergic blockade or the result of the quinidine-like action. The influence of the cardioactive drugs on the isoprenaline-induced phosphorylase activity in the cardiac muscle is decisive in this respect. The influence of propranolol, INPEA, iproveratril and two 1-naphthylethylamine derivatives on the isoprenaline induced phosphorylase activity was studied. Rat hearts were perfused by the method of Langendorff during 20 min. The compounds were infused alone in the range of 0.5–500 μg doses and also 2 min after 0.1 μg isoprenaline (IP) was injected into the perfusion system. Samples of the muscle were taken 30 sec afterwards and the phosphorylase activity was determined. Control hearts were treated with IP alone. IP increased significantly the phosphorylase activity in cardiac muscle as compared with the control. Propanolol completely prevented the effect of IP on metabolism and reduced the mechanical effect of IP. d(—)N- isopropyl-p- nitrophenyl-ethanolamine d(—) INPEA (5 μ g) and l(+) INPEA (50 μg and 500 μg) were ineffective against the IP-induced stimulation of the heart. d(—)INPEA at 50 and 500 μg reduced the effect of IP on phosphorylase activity and blocked completely the pharmacodynamical action of IP on the heart muscle. α-isopropyl- α-[( N-methyl- N-homoveratryl)- α-aminopropyl]-3,4-dimethoxyphenylace-tonitrile (Iproveratril) at 0.5 and 2.5 μg depressed the cardiac activity but not the mechanical or metabolic effects of IP. N-isopropyl- α-methyl- β-1-naphthylethylamine (S-870) (5 μg) and N-propyl- α-methyl- β-1-naphthylethylamine (S-931) (5 μg) did not influence the phosphorylase activity in the heart or the effects of IP.

A study of drug action on the developing avian cardiac muscle

1. 1. A comparative study is described of the responses of the myocardium of the chick at various stages of development to cardioactive drugs. Normal and reserpinized embryos and chicks were empolyed. 2. 2. Tyramine did not exhibit a stimulant action on the embryonic heart prior to the fourteenth day of incubation. The responses to this drug increased with the development of the embryo. 3. 3. Noradrenaline showed both positive inotropic and chronotropic effects on embryonic hearts at all stages of development. 4. 4. A cardiac stimulant extract from ox spleen was investigated. This substance increased the rate and force of contraction of normal hearts as early as the fourth to eighth days of incubation. Hearts at this stage were depressed by tyramine. 5. 5. Reserpinized atria from embryos and hatched chicks were strongly stimulated by the spleen extract and noradrenaline, but were depressed by tyramine. 6. 6. The results indicate that in the early days of incubation noradrenaline is not functionally available for release by tyramine. 7. 7. The results also show that the cardiac stimulant extract of spleen exerts its positive inotropic and chronotropic effects on the myocardium directly.

Death following carotid sinus pressure.

A 66-year-old man with infectious and therapeutic toxicities developed ventricular fibrillation after less than 4 seconds of diagnostic carotid sinus pressure. This is illustrated by an electrocardiogram. A 70-year-old woman with posterior infarction of the heart had carotid sinus pressure applied to correct a tachycardia and developed total cardiac standstill. Both patients died. If the application of pressure to the carotid sinus is being considered for either therapeutic or diagnostic purposes, the authors urge that it be unilateral only, limited to 5-second periods, monitored by auscultation or preferably by electrocardiography, used with special care in elderly patients receiving cardioactive drugs for known cardiovascular disease, and avoided altogether if the initial systolic pressure is below 100 mm. Hg.

DIGITALIS INTOXICATION IN INFANCY AND CHILDHOOD

Ten infants and children with digitalis intoxication, overdosage without symptoms, multiple intoxication with cardio-active drugs and other confusing associated circumstances are reported, including three fatalities. Clinical and electrocardiographic manifestations were not related to the magnitude of the overdosage. Two examples of probable intoxication occurred in children who received digitalis not in excess of the maximum therapeutic doses commonly recommended. The frequent occurrence of congestive heart failure as a manifestation of digitalis intoxication in early life emphasizes the need to consider this cause in the differential diagnosis of cardiac decompensation. Dehydration is cited as a possible factor contributing to the occurrence of digitalis poisoning or if resulting from overdosage, aggravating the intoxication. A wide variety of electrocardiographic disturbances in rhythm and conduction was demonstrated. First degree A-V block occurred in half of the cases. Disturbances in A-V conduction and supraventricular arrhythmias were much more common than abnormalities in ventricular conduction or rhythm. Ventricular arrhythmia was limited to the fatal cases, with one exception. Digitalis therapy in infants and young children requires particular carefulness from all concerned. Whenever possible, the opportunity for error should be minimized by the use of standardized products, familiar to both physician and pharmacist.

Use of external electric pacemaker in cardiac arrest.

Cardiac arrest presents a critical problem in four different types of clinical situations: (1) in Stokes-Adams disease; (2) during reflex vagal stimulation; (3) during treatment with cardioactive drugs; and (4) during various diagnostic and therapeutic procedures, particularly during anesthesia. It requires emergency resuscitation for which the desperate and often ineffective measures of cardiac puncture, intracardiac drugs, and thoracotomy with cardiac massage have been the only therapy heretofore available. 1 We have developed a new therapeutic approach to the problem of cardiac arrest 2 : an externally applied cardiac pacemaker that stimulates the heart electrically, terminates ventricular standstill, and maintains an externally paced ventricular rhythm for as long as necessary. The electric stimulator functions like a natural intracardiac pacemaker but is under complete external control. The instrument is portable, easily applied, and clinically practicable. STOKES-ADAMS DISEASE Stokes-Adams disease consists of attacks of cerebral ischemia due to very slow idioventricular rates, ventricular standstill,

Effect of Heart Rate on Cardiac Membrane Potentials and the Unipolar Electrogram

Effect of Heart Rate on Cardiac Membrane Potentials and the Unipolar Electrogram