Roger F. Palmer

Hydrodynamic Forces in Dissecting Aneurysms IN-VITRO STUDIES IN A TYGON MODEL AND IN DOG AORTAS

It has been argued that pulse wave characteristics are important factors in extension and rupture of acute dissecting aneurysms. To test this, a standard model of an aorta was constructed, consisting of an outer layer of Tygon tubing and an inner layer of rubber cement. An “intimal tear” was produced and the “aorta” was subjected to nonpulsatile and pulsatile flow with increasing increments of pressure. With nonpulsatile flow alone (97 experiments) no dissection occurred at pressures up to 400 mm Hg. Pulsatile flow produced rapid and usually complete dissection with a maximum systolic pressure of 120 mm Hg. The extent of dissection per pulse was related to dp/dtmax in the fluid. No dissection occurred until a critical value of dp/dtmax (790 mm Hg/sec) was reached. Dog aortas were then used in place of the Tygon tube “aorta” with similar results; i.e., dissection did not occur with nonpulsatile flow, but did occur with pulsatile flow (3800 mm Hg/sec). The dissecting dog aorta ruptured to the outside or reentered the vessel lumen. It was concluded that pulse wave characteristics, particularly dp/dtmax, are important in the propagation of dissection.

Ethanol and oral diazepam absorption.

Despite widespread use and abuse of ethanol and diazepam in combination, little is known about the effects of ethanol on diazepam absorption. We administered diazepam (0.07 mg per kilogram of body weight) with water and with 30 ml of 50 per cent ethanol to seven normal volunteers. Plasma diazepam levels were significantly higher at 60 minutes (P less than 0.05), 90 minutes (P less than 0.01), 120 minutes (P less than 0.01), and 240 minutes (P less than 0.01) when diazepam was administered with ethanol than with water alone. Since maximum mean plasma diazepam levels after combined ingestion with ethanol were nearly twice as high than after diazepam and water (373 ng per milliliter versus 197 ng per mililiter at 60 minutes) we conclude that ethanol enhanced diazepam absorption.

The effect of sulfonylurea drugs on rabbit myocardial contractility, canine purkinje fiber automaticity, and adenyl cyclase activity from rabbit and human hearts

Long-term clinical studies have associated tolbutamide therapy with an increased incidence of cardiovascular deaths. The effects of this and other sulfonylurea drugs on contractility and rate of isolated rabbit atria, automaticity of isolated dog Purkinje fibers, and adenyl cyclase activity in particulate preparations of rabbit and human hearts were studied. At concentrations that are attained clinically, tolbutamide (10 mg/100 ml) increased contractility of driven rabbit atria to 124+/-5% of control, acetohexamide (3.9 mg/100 ml) to 140+/-5%, chlorpropamide (8.3 mg/100 ml) to 139+/-6%, and tolazamide (3.1 mg/100 ml) to 119+/-6%. These effects were accentuated in the presence of 2.5 x 10(-4) M theophylline and were not blocked by 1 x 10(-5) M propranolol. Adenyl cyclase was activated by each of these drugs at concentrations below those which increase contractility. The drugs also increased the rate and slope of phase 4 depolarization in spontaneously beating Purkinje fibers, but did not alter the spontaneous rate of isolated rabbit atria. Since inotropic and chronotropic stimulation can be deleterious in some clinical settings, these findings may be of significance in interpretation of cardiovascular mortality data.

Stimulation of Na+ and K+ dependent adenosine triphosphatase by ouabain.

Abstract Ouabain is capable of stimulating as well as inhibiting a microsomal Na + -K + ATPase. Some conditions required for stimulation are outlined and discussed. Evidence is presented that ions are required for ouabain stimulation suggesting that it is a monovalent cation-activated ATPase that is stimulated rather than the Mg ++ ATPase of the preparation. The phenomenon of stimulation by ouabain has properties distinct from those of inhibition. Aging of a preparation of the ATPase results in loss of its ability to be stimulated, but inhibition is preserved. Varying concentrations of K + influence inhibition but not stimulation.

Dissecting aneurysms of the aorta: Present status of drug versus surgical therapy

Abstract Dissecting aneurysm is the most common acute catastrophe involving the aorta, occurring at the rate of about 5 per year per one million population and representing about one in each 500 autopsies. Fewer than 5 per cent of patients with acute dissecting aneurysms of the aorta die immediately and in most patients there is adequate time to make the definitive diagnosis and institute treatment. Intensive drug therapy is the initial treatment of choice in most dissecting aneurysms of the aorta, and particularly so in the acute cases, where the success rate approaches 90 per cent. Surgical therapy should be used in acute dissecting aneurysms only in cases of failure of drug therapy to control hypertension and/or progression of dissection, impending rupture, uncontrollable aortic valve insufficiency, or occlusion of major branches of the aorta. Surgical therapy is indicated electively in the chronic dissection with severe aortic valve insufficiency or enlargement of a localized aneurysm.

The use of propranolol for the protection of turkeys from the development of beta-aminopropionitrile-induced aortic ruptures.

From the Departments of Veterinary Science and Pharmacology and Therapeutics, University of Florida, Gainesville, Florida 32601. This work was supported in part by a grant (H3776) from the National Heart Institute, United States Public Health Service. Florida Agricultural Experiment Stations Journal Series No. 2728. * Markle Scholar in academic medicine. Spontaneous dissecting aneurysms of the aorta occur commonly in both

Beta-aminopropionitrile-induced dissecting aneurysms of turkeys: treatment with propranolol.

Abstract Immature turkeys were fed 0.04% propranolol and 0.07% β-aminopropionitrile (BAPN) for 20 days following the feeding of 0.07% BAPN alone for 15 days (after 3 deaths had occurred from aortic ruptures). There were 2 deaths from aortic ruptures (8.3%) among 24 turkeys fed BAPN-propranolol, and 73.8% mortality from aortic ruptures among those fed BAPN alone. Aortic ruptures resulted from dissecting aneurysms. The feeding of propranolol alone caused no deaths from dissecting aneurysms. There was hypotension and bradycardia among turkeys fed propranolol-BAPN or only propranolol. The histologic and ultrastructural architecture of the abdominal aorta was influenced by the diets consumed. There was profound alteration of the elastic fibers in the tunicae of the aorta when BAPN alone was fed for the entire trial. Alterations of aortic elastic fibers were much less severe when both BAPN and propranolol were fed. The tensile strengths of aortic tissue were highest in turkeys fed only propranolol, and lowest in poults fed only BAPN. Tensile strengths of aortas of turkeys fed BAPN and propranolol were 1.5 times higher than the strengths of arotas of birds fed only BAPN. The efficacy of propranolol as a beta adrenergic blocking agent was indicated by lack of influence of isoproterenol on blood pressure and heart rate of propranolol-treated turkeys. In consideration of the abrupt cessation of mortality that followed propranolol treatment, it is possible that the beneficial therapeutic results achieved with the drug resulted from its influence on both the myocardium and the aorta.

Drug misuse and physician education.

There is little doubt that drugs, old and new, have reduced morbidity and mortality rates and continue to do so. It is dis‐concerting, however, to find that improper medication, polypharmacy, and adverse drug reactions are increasing to the point where drugs, either because of their pharmacologic effects, side reactions, or economic impact on the family unit, constitute what is approaching a national health problem. 2 In some reported series, adverse reactions occurred in 14 per cent of hospitalized patients and 7 per cent of these reactions were fatal or life‐threatening.4 In 5 per cent of admissions to a general hospital, drug reactions were a major factor leading to hospitalization.4

Dissecting Aneurysm of the Aorta as an Unusual Cause of Asthma — An Anatomicopharmacologic Correlation

SINCE the course of acute dissecting aneurysm of the aorta has been dramatically altered by aggressive drug and surgical therapy,1 2 3 unrecognized complications may be unveiled. In the following c...

Management of Acute Dissecting Aneurysms of the Aorta

Survival rates in this most common of catastrophic emergencies involving the aorta have greatly improved with the introduction of intensive drug therapy. The principles of management are applicable in any intensive or coronary care unit; the primary aim is to reduce the force exerted by the pulse wave on the aortic wall, thereby limiting the dissection and allowing healing to take place.