Background-Sublingual nitroglycerin (glyceryltrinitrate, GTN) capsules or isosorbide dinitrate (ISDN) spray are routinely used to treat anginal attacks and to vasodilate maximally the epicardial coronary arteries during coronary angiography. Objective-To compare the coronary vasodilatory eVects of GTN capsules and ISDN spray with those induced by intracoronary GTN using quantitative coronary angiography. Design-96 patients (79 men and 17 women; median age 59 years) were randomised to four groups to receive either a sublingual capsule containing 0.8 mg GTN or two puVs of spray delivering 0.8 mg ISDN, followed or preceded by an intracoronary bolus of 0.2 mg GTN used as reference for maximal vasodilatation. Results-There was a significant increase in the mean diameter of coronary arteries in angiographically normal segments in patients who received either intracoronary GTN (groups 1 and 2) or ISDN spray (group 4) as a first application (group 1, 0.46 mm, +17%, (baseline vessel diameter 100%), p < 0.001; group 2, 0.45 mm, +13%, p < 0.001; group 4, 0.47 mm, +13%, p < 0.05). Patients who received a sublingual GTN capsule as the first application mode (group 3) had no significant change in epicardial vessel diameter (0.10 mm, +5%, p = 0.3). Conclusions-Sublingual ISDN spray may be more eYcacious than sublingual GTN capsules in certain patients with anginal attacks. ISDN spray should be preferred over capsules in coronary angiographic procedures. (Heart 1998;80:365-369) Keywords: angiography; isosorbide dinitrate; nitroglycerin; vasodilatation; angina Organic nitrates are potent vasodilators that are often used therapeutically to treat cardiovascular disease.1 The biochemical basis of their pharmacological action is the release of nitric oxide from the nitrate group, which activates enzyme soluble guanylate cyclase, leading to the accumulation of cyclic guanosine monophosphate and subsequent vascular relaxation. 3Through this mechanism, organic nitrates exert a wide spectrum of physiological actions by dilating peripheral and regional arterial and venous smooth muscle coronary blood vessels, thus increasing coronary blood flow. These eVects lead to a decrease in myocardial oxygen demand and preload as well as an increase in oxygen supply, producing symptomatic relief in angina pectoris and congestive heart failure.4 5 Aside from the biochemical and physiological eVects that are common to all nitrates, individual nitrates differ substantially in their pharmacological potency and pharmacokinetics.6 Experimental work has shown diVerent sensitivity to nitrates in various vessel sections. Sublingual nitroglycerin (glyceryltrinitrate, GTN) capsules or isosorbide dinitrate (ISDN) spray are routinely used to treat anginal attacks and to maximally vasodilate the epicardial coronary arteries during coronary angiography. Alternatively, GTN can be given by the intracoronary route. The safety and eYcacy of these modes of treatment are well established, 7 9 but a controlled comparative study of the eVect of these diVerent ...

The non-sulfhydryl converting enzyme inhibitor Ramipril (HOE 498) is characterized by long lasting antihypertensive activity in man. To examine its cardiovascular potential in heart failure, ramipril was administered during acute ischemic left ventricular failure in pentobarbital anesthetized dogs, induced by repeated injections of plastic microspheres into the left main coronary artery. Repeated embolizations produced stable left ventricular (LV) pump failure characterized by LV enddiastolic pressure of 22 mmHg, reductions in LV dp/dt max and cardiac output. Blood pressure and heart rate were not changed while total peripheral resistance increased. After a stabilization period ramipril was administered in two doses at 30 or 100 micrograms/kg as an intravenous bolus followed by continuous infusion of 3 or 10 micrograms/kg/min for 150 min. Ramipril in the lower dose decreased LV enddiastolic pressure by 8 mmHg, mean pulmonary artery pressure by 4 mmHg, systemic blood pressure by 40 mmHg and total peripheral resistance by 1280 dyn x sec x cm-5. LV dp/dt max, heart rate and cardiac output remained unchanged during ramipril administration. More pronounced effects were obtained with the higher dose. In conclusion, the improvements of hemodynamics produced by ramipril during acute ischemic left ventricular failure in anesthetized dogs are best explained by a reduction in both preload and afterload.

Various methods used for the assessment of infarct-size were compared in a canine model of coronary artery occlusion. The ability of molsidomine (an antianginal agent) to reduce infarct-size was also investigated. Open-chest dogs underwent occlusion of the left anterior descending coronary artery and starting 30 min after the occlusion received either molsidomine (n=8) as an infusion at the rate of 1 microgram/kg/min for 30 min and at a rate of 0.75 microgram/kg/min for 2 h, or saline (controls, n=8). Three hours after the occlusion methylene blue was injected into the left atrium for the assessment of the area at risk in vivo (ARV). The animals were then sacrificed, the heart removed and coronary arteriograms made after injection into the left coronary ostium of a BaSO4-gelatin mass to delineate the post-mortem area at risk (ARPM). The hearts were then cut in sections and the infarct's (I) area visualized with nitroblue tetrazolium C1. The left ventricle (LV) and I were also weighed, ARV, ARPM as well as LV and I areas were determined by planimetry. Body weight and LV mass were similar in both groups, I mass however, was markedly lower in molsidomine than in control dogs. Percentages I/LV mass and area were also significantly lower in the treated than in the control animals, and there was a significant correlation between the mass and planimetric methods for determining I size. ARPM/LV % was similar in both groups and I/ARPM % was smaller in molsidomine than in control animals, however this difference was not statistically significant. Molsidomine markedly reduced ARV/LV % which resulted in similar I/ARV ratios both in the treated and control groups. It is concluded: (1) that the direct measurement of I (mass) or the percentages I/LV mass or area are similarly useful for the detection of a pharmacological effect of I size. ARPM is unaffected by drug treatment and thus provides a valid reference point for the assessment of I. ARV may be altered by a pharmacological intervention and thus may give false negative results when used as the basis for expressing I size. (2) Molsidomine is a potent agent for reducing I size.

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