Sequential hemodynamic changes in end-stage renal disease and the anephric state during volume expansion.

The sequence of hemodynamic events during periods of salt- and water-loading was studied in anephric patients and those with end-stage kidney disease. The 10 patients studied showed four different sequential hemodynamic patterns: 1) no significant increase in blood pressure (BP) in two patients; 2) increase in BP associated with an increase in cardiac output and without change in total peripheral resistance in two patients; 3) increase in BP associated with an increase in total peripheral resistance from the beginning without an increase in cardiac output in five patients; and 4) increase in BP associated with an initial increase in cardiac output followed by an increase in total peripheral resistance in one patient. There was a significant positive correlation between BP and blood volume and between BP and total exchangeable sodium in the patients in whom salt- and water-loading increased the BP. It is concluded that during salt- and water-loading an initial rise in cardiac output is not necessary to increase BP and that a sustained rise in cardiac output does not always increase the total peripheral resistance. Mechanisms other than whole-body autoregulation play a role in increasing BP during salt- and water-loading in patients deprived of renal excretory function.

Dynamics and kinetics of ophthalmic timolol.

Timolol is a beta adrenergic antagonist in 0.25% or 0.5% eyedrop solution for glaucoma. In a double-blind crossover study in healthy males we measured systemic beta blockade, intraocular pressure, and timolol kinetics after the first and ninth 12-hourly dose of a 0.5% ophthalmic solution. Timolol ophthalmic and placebo were each given as 2 drops to each eye with precautions to prevent the normal loss of drug in tears and overflow (high dose) and as 1 drop to each eye with no special precautions (standard therapeutic dose). Exercise tachycardia, measured at 70 and 255 min after administration of drug, was lower at both levels. Postexercise 1-sec forced expiratory volume (FEV1) was not affected. Intraocular pressure measured at 3 and 8 hr after drug was lower at both dose levels. Timolol was consistently present in urine but was not detectable in most plasma samples. Dynamic effects were not greater after the ninth than after the first dose, and the urinary excretion data provided no evidence of drug cumulation.

Diltiazem and propranolol in mild to moderate essential hypertension as monotherapy or with hydrochlorothiazide.

We compared the safety and efficacy of diltiazem and propranolol, and examined demographic factors influencing responses to these agents. One hundred ninety-six patients with supine diastolic blood pressures of 95 to 114 mm Hg were treated with propranolol (80 to 240 mg twice a day) or a sustained-release preparation of diltiazem (60 to 180 mg twice a day) in a double-blind, randomized, parallel group protocol for 6 months. Hydrochlorothiazide was added for patients not achieving the treatment goal. Both agents produced nearly identical and highly significant (p less than 0.001) reductions in supine blood pressure. There were no significant differences at the end of the optional combination therapy phase, although additional reduction with hydrochlorothiazide was slightly greater in the propranolol group. Blood pressure responses in relation to age, gender, race, and smoking history showed that diltiazem produced greater changes in older subjects and women, whereas propranolol was less effective in blacks. However, these differences were not critical.