Effects of antianginal agents on the coronary circulation.
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Biomedical subjects
Publications and source records attributed to D O Williams.
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Seventeen patients presenting with unstable angina pectoris underwent percutaneous transluminal coronary angioplasty (PTCA). Despite vigorous medical therapy, all patients were disabled with 10 experiencing refractory in-hospital angina. PTCA was judged successful in 13 patients and resulted in decreased coronary diameter narrowing from 80 +/- 16% to 34 +/- 13% and reduced transstenotic pressure gradient from 69 +/- 13 to 23 +/- 12 mm Hg. Regional coronary blood flow (CBF) and myocardial metabolism were assessed at rest and during pacing tachycardia in six patients with left anterior descending coronary stenosis. Prior to PTCA, neither regional CBF increased nor coronary vascular resistance declined during rapid pacing; myocardial lactate extraction fell, indicating a shift from aerobic to anerobic metabolism. Following PTCA, however, rapid pacing resulted in increased regional CBF, decreased coronary vascular resistance, and preservation of aerobic metabolism. Following PTCA, successfully dilated patients demonstrated marked relief of angina symptoms, increase in functional capacity, and objective exercise ECG and thallium scintigraphic evidence of relief of previously ischemic myocardium. This investigation demonstrates that PTCA, when combined with medical therapy, can be performed safely and successfully in selected patients who present with otherwise refractory unstable angina, and indicates the procedure deserves further study as a therapeutic alternative in this condition.
The effects of brief and sustained pharmacologic alpha-adrenergic stimulation on the coronary arterial circulation were compared in awake pigs. Phenylephrine was administered into the left anterior descending coronary artery (LAD) either as a bolus (eight pigs) or as a 15-minute infusion (eight pigs), with myocardial blood flow measured by the radioactive microsphere technique. Flow in the distribution in the LAD was compared with flow in myocardium perfused by the left circumflex coronary artery (LCF) as the ratio LAD/LCF. This technique corrects for systemic factors capable of modifying oxygen demand, and hence myocardial blood flow, in both zones. After a phenylephrine bolus (50-100 microgram), LAD/LCF fell significantly, whereas no change was observed after the sustained infusion (5-10 and 50-100 microgram/min). Four additional pigs were pretreated with i.v. adenosine to raise myocardial blood flow in excess of demand before sustained stimulation. In this setting LAD/LCF fell significantly during the sustained phenylephrine infusion. Brief alpha-adrenergic stimulation could overcome normal flow regulatory mechanisms and resulted in constriction of coronary resistance vessels. Such changes did not occur after sustained stimulation and suggest an ability of the coronary circulation to offset chronic vasoconstrictive effects. When the myocardium is overperfused, sustained alpha-adrenergic stimulation does not jeopardize myocardial oxygenation and its vasoconstriction potential is unmasked.
Recent experience has suggested that the ergonovine maleate test is a safe procedure for the diagnosis of variant angina pectoris, because ergonovine-induced coronary vasospasm has generally been reversible by sublingual nitroglycerin. This report describes five cases of ergonovine-induced coronary vasospasm that were refractory to sublingual nitroglycerin. Four of these patients had cardiac arrest. In two patients the vasospasm was responsive to intracoronary nitroglycerin administration. Three patients died as a reuslt of the test. The two survivors differed from the nonsurvivors in the total dose or ergonovine given (0.1 and 0.15 mg versus 0.17, 0.3 and 0.3 mg, respectively) and in the method of administration of ergonovine. The survivors were given serial doses of 0.05 mg each whereas the three nonsurvivors received either larger initial doses (0.1 followed by 0.07 mg) or progressive incremental doses (0.05, 0.1 and 0.15 mg serially). Sublingual nitroglycerin, given to all five patients, and intravenous nitroglycerin, given to three of the five, were ineffective in reversing vasospasm. Intracoronary nitroglycerin favorably altered the course of the survivors. Thus, the ergonovine maleate test is not benign and may cause severe coronary vasospasm that is unresponsive to sublingual and intravenous nitroglycerin, but may be reversed by intracoronary nitroglycerin.
We report 3 cases of polymyositis, confirmed by enzyme assay and muscle biopsy, complicated by serious cardiac disease. They showed progressive fascicular block, despite immunosuppressive therapy sufficient to control the skeletal muscle disease, culminating in complete heart block with syncope, requiring the implantation of a pacemaker. In addition, all 3 showed echocardiographic evidence of dilated cardiomyopathy.
To determine the clinical, angiographic and hemodynamic characteristics of patients with a strongly positive exercise test, 37 subjects demonstrating greater than or equal to 3 mm S-T segment depression were identified among 892 consecutive diagnostic treadmill evaluations. Typical angina by history was present in 78%. 30 patients (81%) had a normal resting electrocardiogram. The strongly positive exercise response was elicited at < 90% of the predicted maximal heart rate in 31 patients (84%). 20% of patients did not experience angina during testing. 20 patients underwent cardiac catheterization. All 20 demonstrated multivessel disease and each had significant stenosis of either the left main (25%) or left anterior descending (95%) coronary artery. Left ventricular function was well preserved.
Regional coronary blood flow and myocardial metabolism were evaluated in a patient who underwent percutaneous transluminal coronary angioplasty (PTCA). Angioplasty increased coronary luminal diameter and reduced trans-stenotic gradient. Before PTCA, angina pectoris developed during sustained rapid atrial pacing and was associated with abnormal lactate metabolism and a mild increase in coronary flow and myocardial oxygen consumption. After PTCA, angina was absent during pacing and lactate extraction was preserved. Coronary flow and oxygen consumption were increased to a greater degree than before PTCA. The temporal response of changes in coronary blood flow due to an abrupt increase in heart rate was also evaluated. Floow reached peak value more rapidly after PTCA. These observations suggest that PTCA may result in improved regional coronary blood flow and restoration of normal flow regulatory mechanism and myocardial metabolism.
Fifty-three patients with chest pain and a negative exercise test at greater than 85% predicted maximal heart rate underwent coronary arteriography. Twenty-one patients (40%) had significant luminal narrowing in one or two vessels. No patient had left main disease. Pathologic electrocardiographic Q waves were present in only coronary heart disease patients (p less than 0.001). There was no difference (p greater than 0.05) in prevalence of T wave abnormalities, chest pain or ventricular beats during exercise in patients with or without coronary disease. Analysis of sex distribution revealed that typical angina pectoris was uncommon in the women (p less than 0.001) and all twenty-one coronary patients were men (p less than 0.001). We conclude that in patients with chest pain and a negative exercise test, three vessel or left main coronary artery disease is unlikely. Also, women with atypical chest pain and a negative exercise test are unlikely to have a fixed coronary obstruction.
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To evaluate the antiarrhythmic efficacy of the new beta adrenergic blocking agent acebutolol, 15 monitored patients with supraventricular arrhythmias received, in double-blind fashion, an intravenous infusion of either acebutolol or saline solution after a control period. Patients treated with saline solution demonstrated no change (P greater than 0.05) in heart rate or arterial blood pressure or conversion to sinus rhythm. After administration of acebutolol, significant (P less than 0.05) reductions in heart rate were noted at 5 minutes. Peak reduction occurred at 10 to 30 minutes and correlated with maximal acebutolol plasma concentrations, antiarrhythmic activity persisted for 24 hours. Mild reductions in systolic blood pressure were observed in the majority of patients. Two patients with atrial fibrillation and one with multifocal atrial tachycardia had conversion to sinus rhythm. Frequent premature atrial complexes noted in one patient were greatly suppressed after administration of the drug. In the nine patients with clinical evidence of chronic obstructive lung disease acebutolol was well tolerated. Adverse reactions were limited to transient dyspnea in one patient with prior heart failure and a decrease in systolic blood pressure to less than 90 mm Hg in three patients who remained asymptomatic. In the patients studied, acebutolol was an effective agent for the treatment of supraventricular arrhythmias and appeared to be of special value in those with chronic obstructive lung disease.
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Myocardial blood flow was studied in 10 closed chest, anesthetized pigs after an acute balloon catheter occlusion of the left anterior descending coronary artery. With use of radioactive microspheres (15 mu), myocardial blood flow was measured before and during an intravenous nitroglycerin infusion and during a combined nitroglycerin-phenylephrine infusion. A significant zone of ischemis (myocardial blood flow less than 50 percent of normal zone flow) was produced by the occlusion and involved 15 percent of the combined left ventricular and interventricular septal mass. More than 50 percent of this ischemic zone was intensely ischemic (myocardial blood flow 0 to 3 percent of normal). Nitroglycerin resulted in a 20 to 30 mm Hg decrease in systolic blood pressure. Myocardial blood flow was unchanged in intensely ischemic areas but varied directly with the product of heart rate and systolic blood pressure in the moderately ischemic area (myocardial blood flow 26 to 50 percent of normal). S-T segment elevation was significantly increased during nitroglycerin infusion and returned to control level with the added infusion of phenylephrine sufficient to restore the systemic blood pressure to prenitroglycerin values. No improvement in ischemic zone perfusion could be demonstrated during the infusion of nitroglycerin alone or with phenylephrine. The endocardial-epicardial flow ratio in moderately ischemic areas was slightly lower than the normal zone flow ratio and decreased slightly during infusion of nitroglycerin. With the addition of phenylephrine, the ratios rose slightly and no longer differed from prenitroglycerin values. Blood flow distribution in acutely ischemic pig myocardium differs considerably from that observed in the dog. Nitroglycerin was not shown to have any beneficial effects with or without its relative hypotensive effect. More extensive study in animal models other than the dog is needed.
Pacemaker malfunction caused by mechanical failure at the site of electrode generator connection has been observed in 5 patients fitted with unipolar pacemakers. Intermittent failure to capture occurred in one patient. The fault was the same in each case and resulted from fracture of a plastic screw designed to hold an insulating cap in place over the electrode generator connection. Changes in impulse amplitude, relative pacing threshold, and distortion of the shape of the pacemaker impulse (overshoot of the leading and trailing limbs and prolongation of the plateau length) occurred in each case, and are helpful in making the diagnosis. In contrast no significant change occurred in the frontal plane axis of the pacemaker impulse. It is concluded that current leaks in unipolar pacemakers can be of sufficient magnitude to cause failure to capture. Early detection is important and is best achieved by examination of the pacemaker signal for amplitude and shape, and assessment of pacing threshold where possible.
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To evaluate the effectiveness of oral vasodilator therapy in chronic congestive heart failure, 20 mg of isosorbide dinitrate or placebo was administered orally in double-blind fashion to 25 patients with congestive heart failure. In 15 patients receiving isosorbide dinitrate, pulmonary arterial wedge pressure decreased 5 minutes to 5 hours after drug administration; the peak reduction was observed at 1 hour (from 23 to 14 mm Hg; P less than 0.001). Wedge pressure decreased to normal (12 mm Hg or less) in 8 of the 15 patients (Group I) but remained greater than 12 mm Hg in 7 (Group II). Reductions in mean systemic arterial pressure, systemic vascular resistance and pressure-time per minute also occurred. Indexes of pump output were unchanged in the 15 who received isosorbide dinitrate but tended to decrease slightly in Group I. Stroke index (from 23 to 26 cc/m2) and stroke work index (from 21.4 to 24.1 g-m/m2) increased slightly but significantly (P less than 0.05) in Group II. Thus the prinicpal hemodynamic action of isorbide dinitrate is marked and sustained reduction in left ventricular filling pressure without pronounced effect on cardiac output. This agent should be used in congestive heart failure primarily for relief of congestive symptoms.
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Small discrete spikes appearing on the electrocardiogram (ECG) of a man with a pacemaker turned out to be fasciculation potentials picked up from leg muscles. To find out how common these spikes were all routine ECGs made in one month were reviewed. Spike potentials were found in six patients, and in each case they originated from somatic musculature. Spikes could nearly always be detected on ECGs that were recorded subsequently in patients known to have lower motor neurone lesions that produced fasciculation. Thus the presence of these fasciculation spikes may suggest underlying neuromuscular disease; this possibility should be recognised by those who record ECGs so that the spikes are not suppressed by overuse of the filter.
In 20 patients with acute myocardial infarction requiring emergency left heart catheterization and coronary arteriography, ventricular function and clinical course were related to collateral vessels supplying the infarcted area. The major coronary artery to the infarcted region was severely obstructed in all patients. Patients with adequate collateral vessels (Group I, no. = 6) and those with no or inadequate collateral channels (Group II, no. = 14) had similar findings with respect to age, site of infarction, prevalence of prior infarction and presence of multivessel disease. However, there were significant differences between Groups I and II in left ventricular end-diastolic pressure (13 versus 30 mm Hg), cardiac index (3.05 versus 2.04 liters/min per m2), stroke work index (45 versus 13 g-m/m2), ejection fraction (42 versus 20 percent) and area of dyssynergy (14 versus 47 percent). Moreover, in Group I all patients survived and none had cardiogenic shock, whereas in Group II 10 of 14 patients had shock and 8 of 14 died. The rapidity of vessel obstruction appeared to influence collateralization since infarction was preceded by angina pectoris more frequently in Group I than in Group II. These results indicate that well functioning anastomotic channels to the distal trunk of the blocked coronary artery may afford some protection of pump function and improve the prognosis in acute myocardial infarction.