Improvement in exercise tolerance and immediate beta-adrenergic blockade with intranasal propranolol in patients with angina pectoris.

A new intranasal spray formulation of propranolol was developed to provide beta-adrenergic blocking medication on an immediate basis to patients with angina pectoris. The effects of this spray or placebo were assessed in 16 patients with effort-induced angina in a blinded, randomized, cross-over design study that compared placebo with intranasal propranolol spray (5 mg/puff) 15 minutes before exercise on a treadmill (Bruce protocol). One week later, each patient, acting as his/her own control, received the alternative treatment and repeated exercise. Mean plasma propranolol level with active therapy was 20 ng/ml. Patients with active spray demonstrated a significant increase in total exercise time than patients taking placebo (530 +/- 197 vs 460 +/- 177 seconds, p = 0.05), an increase in the time to 1 mm ST-segment depression on the electrocardiogram (384 +/- 202 vs 327 +/- 144 seconds, p < 0.05), and an increase in time to onset of angina (452 +/- 149 vs 363 +/- 175 seconds, p = 0.0005). There was a blunting of maximal exercise heart rate with active therapy compared with placebo (120 +/- 13 vs 133 +/- 17 beats/min, p < 0.01), blunting of maximal exercise systolic blood pressure (185 +/- 22 vs 194 +/- 21 mm Hg, p < 0.05), and blunting of peak double product (p < 0.0005), with more modest effects on resting heart rate. Propranolol spray is an effective approach for providing immediate beta blockade and improving exercise tolerance in patients with angina pectoris.

Delay in opening the infarct related coronary artery increases plasma atrial natriuretic peptide levels.

Plasma atrial natriuretic peptide (ANP) levels were measured in rabbits during the late healing phase of myocardial infarcts. Significant differences in plasma ANP levels (P < 0.02) were found between rabbits that had undergone very late (6 h) or early reperfusion (20 and 45 min of ischemia) of the infarct related coronary artery. Differences in ANP levels were independent of infarct size, ventricular remodeling and infarct expansion. We conclude late reperfusion of infarct related artery, independent of myocardial salvage, is associated with increased circulating ANP plasma levels.

Intranasal delivery of cardiovascular agents: an innovative approach to cardiovascular pharmacotherapy.

The intranasal administration of drugs has long been used for the topical treatment of various nasal disorders. Many features of the intranasal mucosa also make it useful for delivery of systemically active agents. It has been shown that intranasal drug administration can provide plasma drug levels similar to those observed with comparable doses of parenteral drugs. The feasibility of intranasal administration of propranolol, nifedipine, and nitroglycerin has been investigated in several small clinical studies. Intranasal propranolol has been shown to improve exercise tolerance in patients with angina pectoris. Intranasal nifedipine has been used to treat patients with perioperative hypertension and hypertensive crisis. Intranasal administration of nitroglycerin was shown to blunt the hypertensive response to endotracheal intubation. These studies and others suggest that intranasal delivery of cardiovascular drug treatment could be used in those clinical situations where a rapid or intermittent drug effect is desired and can potentially serve as an alternative to parenteral drug administration.

Spinal cord sarcoidosis: a case report and review of the literature.

Sarcoidosis is a multisystem syndrome characterized by the development of noncaseating granulomata. These lesions disrupt the architecture and function of the tissue in which they reside. Sarcoidosis in and around the spinal cord is relatively rare. This article discusses a patient with sarcoidosis who presented with progressive spinal cord compression. Neurosarcoidosis can occur with manifestations involving the cranial nerves, parenchymal brain tissue, neurohormonal axis of the base of the brain, spinal cord, or peripheral nerves. When the spinal cord is involved, it is most important to determine the location and confirm the diagnosis. Intramedullary lesions respond to medical therapy alone, if at all. Extramedullary lesions may be amenable to surgical resection with postoperative steroid therapy. If treated in time, patients with the latter form generally achieve a nearly full recovery.

Angiotensin II receptor antagonists: a new approach to blockade of the renin-angiotensin system.

A-II exerts its activity on various target tissues by binding to its receptors. The discovery of local RASs and A-II receptors within various tissues has generated interest in the clinical usefulness of RAS inhibition by directly blocking the action of A-II at the receptor level. Different A-II receptor subtypes have been identified and subsequently termed AT1 and AT2. AT1-receptor subtypes are the predominant receptor subtypes existing in most organs and, by coupling to a transmembrane G protein, seem to be the main subtypes participating in the vasoactive responses of A-II. Saralasin, a peptide with specific A-II receptor-antagonistic activity, had limited practical long-term usefulness as a result of its short half-life, significant agonistic properties, and lack of oral bioavailability. The discovery of simple benzyl-substituted imidazoles, which possess weak but highly selective A-II receptor antagonistic properties, led to the development of losartan (DuP 753). Losartan is a potent, orally active, specific, competitive nonpeptide A-II receptor antagonist that appears to be an effective antihypertensive agent both in animal studies and in preliminary clinical trials. The therapeutic usefulness of losartan, however, is not limited to its antihypertensive effects. The potential benefits of A-II receptor antagonists include roles in postmyocardial infarction therapy, slowing A-II-induced cardiac hypertrophy, 154, 155 slowing the progression of heart failure, preventing postangioplasty restenosis, and in slowing the progression of renal disease. Furthermore, losartan, a selective A-II type 1 (AT1) receptor antagonist, has also been a valuable pharmacologic probe for studying the mechanism of A-II stimulation of its receptors. A-II receptor antagonism appears to be as effective as ACE inhibition in the treatment of hypertension and other pathologic processes that involve the RAS and may offer an alternative to those patients who cannot tolerate ACE inhibitors because of their side effects.

Apical hypertrophic cardiomyopathy. A case report.

The clinical, ECG and angiographic features of apical hypertrophic cardiomyopathy in a 24-year-old white man are reported. Only 4 non-Oriental cases have so far been described and the present case is the second from South Africa. Attention is drawn to the possibility that there are two distinct types of apical hypertrophic cardiomyopathy.