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Biomedical subjects

D C Harrison

Publications and source records attributed to D C Harrison.

At least 91 records · Page 5Linked to original sources

Anatomically flexible, computer-assisted reporting system for coronary angiography.

A computer-assisted method for reporting coronary arteriographic findings has been developed. A videographic display with a touch input system permits finger pointing to designate arterial segments, lesion locations, graft insertion points and collateral vessels. The coronary diagram is flexible to accommodate variations in dominance and in the size and length of the left coronary system branches. Lesion severity, type and length of lesions, distal vessel anatomy, collateral circulation and coronary bypass grafts (including Y or jump grafts) are displayed pictographically. A tabular summary and graphic output provide a completed coronary report eliminating the need for narrative dictation. An edit mode provides capability for teaching and review. The computer-assisted reporting method has the advantage of automatic data encoding in formats suitable for data base storage and subsequent retrieval.

Angiography↗

A new catheter system for coronary angioplasty.

A new catheter system has been designed for percutaneous transluminal coronary angioplasty. An independently movable, flexible-tipped guide wire within the balloon dilation catheter facilitates selection of the involved vessel. This guide wire can be passed slowly and carefully beyond the coronary stenosis, permitting safe advancement of the balloon catheter. After testing in animal and cadaver hearts, this system was used in 53 patients (56 stenoses) with single vessel coronary artery disease, with an overall primary success rate of 64 percent. In the last 41 of these 56 cases, use of a balloon catheter with a smaller deflated diameter increased the success rate to 73 percent. In patients with lesions of the left anterior descending coronary artery, the success rate was 89 percent. Three (6 percent) of the 53 patients had complications during coronary arterial dilation that necessitated emergency coronary arterial bypass graft surgery. There were no procedure-related or late cardiac deaths. During the mean follow-up period of 8 months (range 1 to 21), there were one late death (of noncardiac causes) and no late myocardial infarctions. Clinical status was persistently improved in 31 of the 36 patients who had successful dilation. The remaining five patients experienced restenosis at the angioplasty site and return of angina pectoris within 3 months of dilation. Two of these patients had repeat coronary angioplasty with restoration of asymptomatic status, and three had elective coronary bypass graft surgery.

Angioplasty, Balloon↗

Prolongation of verapamil elimination kinetics during chronic oral administration.

The elimination of verapamil and its n-demethylated metabolite, norverapamil, was studied in nine patients with chronic atrial fibrillation after the first oral verapamil dose and during chronic oral verapamil administration. Significant increases (p less than 0.01) were seen in the elimination half-lives (t 1/2's) of both verapamil (6.4 +/- 3.5 to 12 +/- 5 hours, mean +/- SD) and norverapamil (10.3 +/- 6 to 16.5 +/- 7 hours) during chronic oral verapamil administration. These pharmacokinetic observations have important clinical implications for the rational long-term administration of this agent. Once steady-state serum concentrations have been achieved during chronic verapamil administration, verapamil doses should be given at less frequent intervals or in smaller doses in order to produce the desired serum concentration and therapeutic response and to minimize unwanted or toxic drug effects.

Administration, Oral↗

Acute hemodynamic effects of intravenous encainide in patients with heart disease.

Encainide, a new antiarrhythmic drug, was given intravenously (0.9 mg/kg) to 18 patients over 15 minutes to evaluate the hemodynamic effects. Hemodynamics and drug plasma concentrations were measured during and 30 minutes postdrug infusions. Encainide infusion was associated with a decrease in cardiac index from 2.6 +/- 0.7 to 2.4 +/- 0.7 L/min/m2 (p less than .05), a significant decrease in stroke work index and left ventricular end-diastolic pressure, and with a rise in systemic vascular resistance. There was no change in systemic or pulmonary arterial pressure, left ventricular dp/dt, or pulmonary vascular resistance. The patients were studied 30 to 60 minutes after cardiac angiography. Comparison of hemodynamic values obtained preangiography with those obtained postangiography (before, during, and after drug infusion) strongly suggests that many of the observed effects were due to radiographic contrast media (initial osmotic volume loading and subsequent diuresis). We conclude that if encainide has any significant hemodynamic effects after intravenous use, it is a modest decrease in cardiac output, possibly as a result of decreased left ventricular filling pressure.

Adult↗

Randomized double-blind comparison of nifedipine and isosorbide dinitrate therapy in variant angina pectoris due to coronary artery spasm.

Twelve patients were entered prospectively into a randomized double-blind study comparing the efficacy of nifedipine and isosorbide dinitrate (ISDN) in the treatment of variant angina pectoris due to coronary artery spasm. Using the diary technique, both anginal episodes and nitroglycerin tablets consumed were recorded during the pretrial, no drug period, and both active drug phases. During the baseline pretrial period, an average of 1.1 anginal episodes/day occurred with reduction to 0.28/day during nifedipine treatment and 0.39/day during ISDN treatment. Headache was the major side effect during ISDN treatment, occurring in 9 of 11 (81%) patients; and nonheart failure related pedal edema during nifedipine treatment, occurring in 4 of 12 (33%) patients. Intolerable side effects necessitating cessation of treatment occurred in two patients during nifedipine treatment and in three patients during ISDN treatment. Patients preferred nifedipine over ISDN because of increased efficacy and fewer uncomfortable side effects. We conclude that both nifedipine and ISDN are effective therapy for coronary spasm, but that nifedipine was more effective and was preferred by the majority of patients.

Adult↗

Prolongation of the human cardiac monophasic action potential by sotalol.

Sotalol and propranolol are nonselective beta-adrenergic blocking agents. Sotalol at low concentration, unlike propranolol, prolongs the duration of the transmembrane action potential. In a double-blind study, the electrophysiologic effects of intravenous sotalol (0.30 or 0.60 mg/kg; n = 9) were compared with intravenous propranolol (0.15 or 0.20 mg/kg; n = 8) in 17 patients with use of bipolar suction electrodes in the right atrium and right ventricle to determine whether sotalol prolongs the monophasic action potential duration in man. After administration of sotalol, there were significant increases (paired t test) in the Q-T interval (p less than 0.001), right atrial effective refractory period (p less than 0.05), right ventricular effective refractory period (p less than 0.005), right atrial monophasic action potential duration at 90% repolarization (p less than 0.01), and right ventricular monophasic action potential duration at 90% repolarization (p less than 0.005). Prolongation of the monophasic action potential duration was dependent on plasma sotalol concentration. There were no significant changes in these variables after propranolol. The spontaneous cycle length and Wenckebach cycle length increased significantly in both groups, and the mean blood pressure decreased in both, although not significantly after propranolol. In summary, sotalol but not propranolol prolonged atrial and ventricular effective refractory periods and lengthened the monophasic action potential and the Q-T interval of human myocardium after intravenous infusion. The ability to acutely prolong repolarization at therapeutic plasma concentration is unique among known competitive beta-adrenergic receptor antagonists.

Action Potentials↗

Simultaneous measurement of coronary venous blood flow and oxygen saturation during transient alterations in myocardial oxygen supply and demand.

Continuous simultaneous measurements of coronary venous oxygen saturation and coronary venous blood flow were performed in 10 open chest dogs and 13 conscious human patients, using a combination of fiberoptic oximetry and thermodilution. Measurements were made during transient coronary arterial occlusion and during the intracoronary administration of nitroglycerin or isoproterenol. Two patterns of coronary vasodilation were distinguished: in primary (demand-independent) vasodilation, both coronary flow and coronary venous oxygen saturation increased, while myocardial oxygen consumption remained constant. In secondary (autoregulatory) vasodilation, coronary flow increased as coronary venous oxygen saturation decreased, corresponding to an increase in myocardial oxygen consumption. These observations could not have been made if either coronary venous blood flow or oxygen saturation had been measured alone; thus, this investigation demonstrates the utility of this combination of techniques in the study of the coronary circulation.

Animals↗

Metabolite cumulation during long-term oral encainide administration.

Cumulation of encainide and its major metabolites, O-demethylencainide (ODE), 3-methoxy-ODE (MODE), and N-demethylencainide (NDE) was examined in patients with frequent complex ventricular ectopy. After 6 mo on encainide patients were admitted to Stanford University Hospital and the drug was discontinued for 24 hr. During this time blood samples were drawn to characterize the cumulation and disposition of the drug and metabolites. The mean steady-state concentrations of encainide, ODE, and MODE were 56.3, 214.6, and 184.6 ng/ml after doses ranging from 100 to 250 mg/day. The concentration ratios of ODE/encainide and MODE/encainide were 5.02 +/- 2.61 and 5.15 +/- 4.13. NDE was detected in the plasma of only one patient. Elimination half lifes of encainide and ODE were 1.16 +/- 0.5 and 11.41 +/- 9.58 hr. MODE disappeared slowly and at 24 hr the plasma concentration was still 59.8 +/- 39.9% of its mean steady-state concentration. Our data indicate that the metabolites of encainide cumulate in the plasma of patients on long-term oral therapy and must be considered when evaluating its clinical efficacy.

Administration, Oral↗

The effects of diltiazem and reduced serum ionized calcium on ischemic ventricular fibrillation in the dog.

Calcium influx blockers reportedly suppress ventricular arrhythmias during acute ischemia. We therefore studied the effects of diltiazem and reduced serum ionized calcium on ventricular fibrillation (VF) in a reversible ligation model. VF was produced at 15-minute intervals by simultaneous occlusion of the left anterior descending and circumflex arteries of 31 dogs. Time from coronary occlusion to onset of VF showed no significant variation during 15 consecutive trials in six dogs that received saline alone. Intravenous infusion of diltiazem (0.02 mg/kg per min) markedly delayed the onset of VF in each of 10 dogs (P less than 0.0001). Mean VF latency increased from 138 to 295 seconds during a 45-minute diltiazem infusion, declined exponentially when the infusion ceased, and was strongly correlated with serum diltiazem concentration (r = 0.96, P less than 10(-6)). In five dogs, hemodynamic measurements, including coronary venous blood flow, were performed during each occlusion. The increase in VF latency by diltiazem was not due to increased coronary flow during occlusion or to reduction of left ventricular (LV) mechanical work. In six dogs, mean serum ionized calcium, [Ca++], was reduced from 1.11 to 0.59 mM by infusion of sodium citrate. Citrate infusion increased mean VF latency from 155 to 243 seconds, and the increase observed in each dog was correlated (r = 0.84, P less than 10(-6)) with the reduction in [Ca++]. VF latency was unaffected by lidocaine in nine dogs. The antifibrillatory effect of diltiazem during global LV ischemia may be an electrophysiological phenomenon related to reduction of cellular calcium influx.

Animals↗

Histamine provocation of clinical coronary artery spasm: implications concerning pathogenesis of variant angina pectoris.

Twelve patients with nonexertional chest pain and nonobstructive fixed coronary disease (less than 50% luminal diameter narrowing) were given histamine to investigate the potential role (coronary artery H1 receptor agonism) of the endogenous agent in producing coronary artery spasm (CAS). Histamine, at intravenous dose of 0.5 to 1.0 microgram/kg/min, provoked CAS in four patients. In six patients neither histamine nor ergonovine provoked spasm, and these patients were considered by chronic follow-up evaluation to have noncardiac etiology for their chest pain syndrome. In one patient CAS was provoked with ergonovine but not by histamine, and one ergonovine-positive patient had an equivocally positive histamine result. Pretreatment with cimetidine (H2 receptor antagonism) was necessary to avoid unpleasant side effects of histamine. Thus these observations indicate that histamine should be included among the specific agents capable of inducing CAS and provide new insight concerning the mechanism(s) causing variant angina pectoris.

Adult↗

Application and safety of outpatient ergonovine testing in accurately detecting coronary spasm in patients with possible variant angina.

We analyzed the results of 61 consecutive outpatient ergonovine provocation tests to determine the safety and efficacy of such outpatient testing for detecting coronary artery spasm (CAS). Criteria for outpatient testing included: clinical history suggestive of variant angina, noncritical coronary artery disease documented by coronary arteriography, normal exercise treadmill test, no symptomatic arrhythmias, and no history of recent myocardial infarction. All antianginal medications were tapered and stopped. Ergonovine maleate was given as a bolus at 3-minute intervals in consecutive doses of 0.05, 0.10, and 0.25 mg. A positive test was defined as chest pain accompanied by greater than 0.1 mV ST segment elevation of 12-lead ECG. If pain and ST-segment elevation occurred, intravenous and sublingual nitroglycerin were immediately administered for relief of myocardial ischemia. Of the 61 patients studied, 10 had positive tests; there were no complications. Follow-up the 51 patients with negative studies has not revealed cardiac etiology for their chest pain. We conclude that outpatient ergonovine testing is a safe and accurate diagnostic test for identifying CAS in a highly selected population of patients with possible variant angina when performed under carefully controlled conditions.

Adult↗

Long-term benefit of cardioselective beta blockade with once-daily atenolol therapy in angina pectoris.

The long-term efficacy of once-daily atenolol cardioselective beta-blockade therapy for chronic stable angina pectoris was studied in nine coronary disease patients. After a placebo-controlled single-blind dose-ranging trial with 2-week drug periods of 25, 50, 100, and 200 mg, they continued on 100 or 200 mg daily for 1 year. Treadmill exercise test (ET) were performed at times at peak and trough serum atenolol concentrations and 24-hour ECG ambulatory recordings were obtained after placebo, after 2 weeks of 100 and 200 mg atenolol, and after 2 weeks of 100 and 200 mg atenolol, and after 3, 6, 9, and 12 months of 100 or 200 mg atenolol. During early and chronic atenolol therapy, angina frequency and nitroglycerin consumption were decreased (p less than 0.01 to less than 0.001). Twenty-four hour ECG and ET showed sustained heart rate suppression. Exercise duration until angina onset was prolonged during all periods of atenolol administration. Maximal improvement in exercise tolerance and angina relief was not reached until 3 months of atenolol therapy despite stable serum drug concentrations. During the 14 months fatigue occurred in three patients which was dose-limiting in only one. Thus atenolol 100 or 200 mg given once daily, proved well-tolerated and potent anti-ischemic myocardial actions which were effectively maintained during chronic therapy of angina pectoris.

Adrenergic beta-Antagonists↗