/pdf/studies-on-digitalis-iv-observations-in-man-on-the-effects-1v20xswh1a.pdf

Studies on digitalis. iv. observations in man on the effects of digitalis preparations on the contractility of the non-failing heart and on total vascular resistance.

The cardiotonic activity of a new, noncatechol, nonglycoside agent, amrinone, was investigated in vitro and in anesthestized and unanesthetized dogs. Amrinone (3-100 microgram/ml) caused a dose-dependent increase in papillary muscle developed tension and df/dt without significant changes in duration of the contractile cycle or time-to-peak tension. Amrinone induced slight increases in right atrial rate with no changes in electrophysiological properties of the cat papillary muscle or dog Purkinje fibers. In anesthetized dogs, intravenous bolus injections of amrinone at doses ranging from 1 to 10 mg/kg caused increases in cardiac contractile force and left ventricular dp/dt max with relatively small changes in heart rate and blood pressure. No significant changes in lead II ECG were observed. In unanesthetized dogs, intravenous infusion of amrinone (10-100 microgram/kg per min) caused increases in left ventricular dp/dt max and only small changes in heart rate and blood pressure. Amrinone, tested orally in this model at doses of 2-10 mg/kg, produced a positive inotropic effect with a rapid onset and long duration of action. The inotropic response to amrinone was not blocked by propranolol, dibenzyline, chlorisondamine, atropine, metiamide, or reserpine. Amrinone's inotropic response was not associated with significant alterations in cardiac norepinephrine, phosphodiesterase, cyclic AMP, or Na+, K+-activated ATPase.

Cardiotonic activity of amrinone--Win 40680 [5-amino-3,4'-bipyridine-6(1H)-one].

The regulation of the performance of the heart.

/pdf/studies-on-digitalis-i-direct-effects-on-peripheral-vascular-3jzuvkzjx5.pdf

Studies on digitalis. i. direct effects on peripheral vascular resistance

In spite of the widespread use of digitalis in clinical medicine and the extensive experimental work that has been carried out with this drug, its action on the nonfailing human heart still requires clarification. A variety of experiments on openchest, presumably normal, anesthetized dogs has clearly shown that digitalis glycosides have a positive inotropic action (1-4). The applicability of these observations to the normal heart in intact human subjects is limited because the possibility cannot be excluded that depression of myocardial contractility by the anesthetic agents and the surgical exposure of the heart modified the response to the digitalis glycoside in the animal experiments. Hemodynamic studies in subjects with normal hearts and in patients with heart disease without congestive heart failure have suggested that digitalis does not improve myocardial contractility, and may even have a depressing effect, since its administration results either in no change in the cardiac output, or in a decline (5-9). It is now clear that measurement of the cardiac output alone does not necessarily provide an assessment of ventricular contractility (10). The unavailability, in the past, of a reliable method for studying contractility in the hearts of intact human subjects has been responsible for the lack of information concerning the crucial question of how digitalis affects the normal, or the diseased but nonfailing human heart. Recently, Sarnoff and Mitchell have defined myocardial contractility as follows: "When from any given end-diastolic pressure or fiber length, the ventricle produces more external stroke work and more external stroke power, an increase in ventricular contractility is said to have taken place. Implicit in this definition is an increased rate of development of tension when contractility increases" (11). Rushmer has also found that an increased ventricular contractility is reflected bvy an increase in the peak rate of development of intraventricular pressure (12). The observations of these and other investigators (1, 4, 13-19) are all compatible with the view that the rate at which ventricular pressure rises during isometric contraction is determined by the contractile state of the myocardium and by the conditions under which the ventricle contracts, i.e., the ventricular enddiastolic pressure, arterial pressure, and heart rate. In 1927, Wiggers and Stimson demonstrated that digitalis resulted in a more rapid rise of left ventricular pressure in the dog, and they concluded that, like epinephrine, the glycosides improve myocardial contraction (1, 16). Measurement of the instantaneous rate of rise of intraventricular pressure in man has been fraught with considerable difficulty because of the serious artifacts in the pressure tracings obtained at cardiac catheterization by the standard catheter-manometer systems. The recent development of a cardiac catheter with a high-fidelity micromanometer mounted at its tip (20), however, has largely solved this problem, since it is now possible with this instrument to record intraventricular pressure pulses faithfully and without significant distortion. In a previous communication from this laboratory, the use of the continuously computed rate of change of intraventricular pressure in assessing the functional status of the heart in man was presented (21). The objective of the present investigation was to apply this technic in the determination of the effects of a cardiac glycoside, ouabain, on the normal and on the diseased but nonfailing human ventricle.

/pdf/studies-on-digitalis-ix-effects-of-ouabain-on-the-nonfailing-34mq8xvbsa.pdf

Studies on digitalis. ix. effects of ouabain on the nonfailing human heart.

Ouabain induces a moderate increase in the contractility of the nonfailing heart of the dog with a complete circulatory system in doses which do not produce electrocardiographic signs of digitalis ...

Action of digitalis on the nonfailing heart of the dog.

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Action of digitalis on the nonfailing heart of the dog.