Digital plethysmography for assessing erythrityl tetranitrate bioavailability.

The bioavailability or oral, sublingual, and chewable tablets or erythrityl tetranitrate (ETN) was evaluated in 15 normal men. In a randomized, complete crossover investigation with nitroglycerin and placebo controls, drug-induced changes in the diastolic amplitude response intensity were measured with a digital plethysmogram. Values for area under the response intensity curve (AUC), maximum response intensity (Imax), and time lapse from dosing to peak response (tmax) were obtained by computer processing and converted to intensity values and AUC segments for specific time intervals. Sublingual nitroglycerin induced a response (p less than 0.05) from placebo within the first hour. Although somewhat slower in reaching peak intensity, all forms of ETN induced significant responses over placebo (p less than 0.05) for 2 hr, with oral (swallowed) ETN different 6 hr. Our results indicate that all the ETN dosage forms were bioavailable, with the longest duration of effect by the oral form.

[Vasodilator treatment of chronic heart failure: a chronic double-blind trial with prazosin and erythrityl tetranitrate]. / Lechenie na khronichnata surdechna nedostatuchnsot s vazodilatoatori--khronichen dvoino sliap opit s prazozin i eritritiltetranitrat.

A chronic double-blind experiment was carried out with 32 patients with severe chronic stasis cardiac insufficiency, with concomitant idiopathic congestive cardiomyopathy and ischemic heart disease, in assessing the effect of vasodilators prazosin or erythrityl tetranitrate upon the decompensation symptomatics and hemodynamic indices. The clinical indices of cardiac insufficiency with hemodynamic signs of pre-loading, myocardial contractility and postloading of left ventricle were followed up. Besides vasodilators the patients were administered the ordinary maintenance therapy with digoxin and diuretics. The experiment was a double blind one, controlled by placebo-periods and covered a 6 months follow-up period. The combined venous-arteriolar vasodilator prazosin was reduced pre and post-loading, it increased the cardiac output, without essential changes in functional capacity of the patients with chronic cardiac insufficiency. Erythrityl tetranitrate, however, has no substantial effect on the clinical and hemodynamic indices of statis cardiac insufficiency even in higher doses. That suggests the necessity of the chronic cardiac insufficiency treatment to be carried out with vasodilators with venous and arteriolar effect.

Medical therapy of angina pectoris.

The pathophysiology of angina pectoris is best understood as an imbalance between oxygen supply and demand. The primary determinants of myocardial oxygen demand are heart rate, arterial pressure, heart size, myocardial contractility, and myocardial mass. The medical therapy of angina pectoris is directed toward reducing myocardial oxygen demand by reducing the workload of the heart and the specific determinants listed. The most common medications used in the treatment of angina pectoris are nitroglycerin and propranolol. Nitroglycerin reduces myocardial oxygen demand primarily by reducing heart size and arterial pressure. Propranolol reduces oxygen demand primarily by reducing heart rate. Medical therapy is generally effective in controlling the symptoms of angina pectoris in 80% or more of the patients and allows them to lead useful and productive lives.

Contractile state of the left ventricle in man as evaluated from end-systolic pressure-volume relations.

End-systolic pressure (PES), volume (VES), wall tension (TES) and circumference (CES) of the human left ventricle were studied at cardiac catheterization in 24 subjects with varying degrees of left ventricular dysfunction. Acute alterations in systolic load consistently resulted in changes in VES and CES, with a smaller volume and circumference characterizing the lower systolic load in each subject. End systolic pressure-volume lines were constructed by plotting PES against VES at the higher and lower systolic load in each subject. The slope of the resultant lines was considerably steeper for normal than for poorly contractile left ventricles. Vo, the volume axis intercept of the line (i.e., the theoretical VES at PES = O) was significantly smaller for normal than for poorly contractile ventricles. Similar findings were noted for Co, the theoretic end-systolic circumference at zero end-systolic ventricular wall tension. Post-extrasystolic potentiation resulted in decreased VES and CES with no change in PES and only a slight fall in TES. In conclusion, end-systolic pressure-volume and tension-circumference relations reflect the contractile state of left ventricular myocardium. Quantitation of these relationships may provide a useful new approach to the assessment of myocardial function in man.