A Possible Application of Vasodilatators in Acute Coronary Occlusion

Abstract

Although 100 years has elapsed since the introduction of the nitrates and nitrites for the treatment of angina pectoris and coronary insufficiency, they are still not recommended for therapy, in the events following an actual coronary occlusion .1-4 The fact that these chemical compounds were found to be superbly effective agents for relief of the complex physiologic syndrome of angina pectoris long before its basic mechanisms were partially known or investigated is not unusual in the annals of medical history. However, the additional fact that their action on the heart of coronary artery vasodilatation, reduced cardiac work, reduced myocardial oxygen requirement, and/or increased oxygen delivery to the myocardium has not found a practical application in the treatment of coronary thrombosis is a paradox in itself. The past difficulties of toxicity in the use of these drugs may be at fault, especially their tendency to produce hypotension and methemoglobinemia when given in large amounts. The current availability of the newer nitrate and nitrite compounds offering a prolonged action at a low dosage, without producing significant vasodepression, makes a re-evaluation of this subject worthwhile.To test this hypothesis further, we have endeavored to influence a favorable outcome following the ligation of the left coronary artery in dogs at a point which almost uniformly produces a fatal result. By the use of a long acting nitrate, during only the early stages of the artificially produced myocardial infarct, we have attempted to establish whether a beneficial action can be reflected in the over-all mortality figures.In addition we are reporting some preliminary experiences with the use of this compound in proved human cases of coronary thrombosis with myocardial infarction. METHODSMongrel dogs with weights between 26 and 36 lb (12 to 16 kg) were used. All animals were previously vaccinated against distemper and were in good health at the time of the procedure. Intravenous pentobarbitol was used as the anesthetic agent. Sterile preparations were made for thoracotomy and arterial and venous cutdowns used in measuring blood pressure and infusing medications. Lead II of an electrocardiogram was monitored on all preparations prior to and at intervals during the procedure. The initial preparations included the insertion of a 16-gauge polyethylene catheter into both the femoral artery and vein, and extending these into aorta and vena cava. The arterial canula was then connected to a strain gauge, and thence to a Sanborn multichannel amplifier for recording blood pressure. Electrocardiograms were taken on the same machine, coincident with the pressure tracings.A left thoracotomy incision was made by entering the chest through the 4th or 5th interspace. The incision was approximately 10 cm in length, and was initiated at the sternal margin. This allowed more than adequate exposure to the left coronary artery distribution and yet could be easily and rapidly closed. The left lung was retracted, and the pericardial sac opened par...

Modification of the size of developing infarcts in the ligated dog heart by betahistine-HCL

“…Early investigators [Wiggers and Green, 1936;Zolland Norman, 1952;Kattus el a!., 1959] showed that a variety of drugs including papaverine, sodium nitrite and nitroglycerine had little effect on the collateral circulation. Hedges et al [1961] demonstrated in a small group of dogs that isosorbide dinitrate, when administered after total ligation of the circumflex artery, increased survival from 43% in controls to 100% in the experimentáis. Slejeskog et al [1963], however, showed that isosorbide dinitrate was not effective in the treatment of acute coronary artery ligation in the baboon due to the systemic hypotension caused by the drug.…”