Aortic input impedance during nitroprusside infusion. A reconsideration of afterload reduction and beneficial action.

Beneficial effects of nitroprusside infusion in heart failure are purportedly a result of decreased afterload through "impedance" reduction. To study the effect of nitroprusside on vascular factors that determine the total load opposing left ventricular ejection, the total aortic input impedance spectrum was examined in 12 patients with heart failure (cardiac index <2.0 liters/min per m(2) and left ventricular end diastolic pressure >20 mm Hg). This input impedance spectrum expresses both mean flow (resistance) and pulsatile flow (compliance and wave reflections) components of vascular load. Aortic root blood flow velocity and pressure were recorded continuously with a catheter-tip electromagnetic velocity probe in addition to left ventricular pressure. Small doses of nitroprusside (9-19 mug/min) altered the total aortic input impedance spectrum as significant (P < 0.05) reductions in both mean and pulsatile components were observed within 60-90 s. With these acute changes in vascular load, left ventricular end diastolic pressure declined (44%) and stroke volume increased (20%, both P < 0.05). Larger nitroprusside doses (20-38 mug/min) caused additional alteration in the aortic input impedance spectrum with further reduction in left ventricular end diastolic pressure and increase in stroke volume but no additional changes in the impedance spectrum or stroke volume occurred with 39-77 mug/min. Improved ventricular function persisted when aortic pressure was restored to control values with simultaneous phenylephrine infusion in three patients. These data indicate that nitroprusside acutely alters both the mean and pulsatile components of vascular load to effect improvement in ventricular function in patients with heart failure. The evidence presented suggests that it may be possible to reduce vascular load and improve ventricular function independent of aortic pressure reduction.

Re-thinking angina.

William Heberden in 1772 published "some account of the disorder of the breast" which contains the essential elements of angina pectoris as we understand it today. The number of existing cases in the U.S. population today is 6.4 million. Myocardial ischemia manifested by angina pectoris can be either acute or chronic. Patients with chronic stable angina will be the focus of this supplement. The majority of patients are symptomatic but approximately 25% can be asymptomatic. The clinical manifestations of myocardial ischemia generally are chest discomfort, arrhythmias, and LV dysfunction. Myocardial ischemia is a result of imbalance between myocardial oxygen supply and myocardial oxygen demand. High grade coronary stenosis are the usual cause of decreased oxygen supply. The classic hemodynamic factors increasing myocardial oxygen demand include hypertension and increased heart rate due to tachyarrhythmias of any etiology. Exertion is the usual precipitating cause of chronic myocardial ischemia. New information has come forward indicating that myocardial ischemia is associated with disruption of cellular sodium and calcium homeostasis. Ischemia results in a rise of intracellular sodium concentration and thus sodium overload which then activates the sodium calcium exchanger and leads to increased intracellular calcium. When this occurs there is electrical instability and mechanical dysfunction which increases oxygen demand and decreases oxygen supply. The compound Ranolazine is thought to selectively inhibit the late sodium current and attenuates the abnormalities of ventricular repolarization and contractility associated with myocardial ischemia. This compound is the first new class of anti-anginal medication approved in 25 years which may provide physicians with additional therapy for chronic stable angina along with the other anti-angina agents, beta blockers, calcium antagonists and nitrates.

Treatment of mechanical valve thrombosis during pregnancy.

Pregnant patients with mechanical valves require anticoagulation. The risk of bleeding and embryopathy associated with oral anticoagulation must be weighed against the risk of valve thrombosis. In the presence of a mechanical valve thrombosis, an appropriate treatment modality must be selected, as it is critical for the health of mother and fetus. In this review, we present a pregnant patient with mechanical valve thrombosis (MVT) who underwent thrombolytic therapy, subsequent anticoagulation according to available guidelines, and delivered a healthy baby at full term.

Inhibition of sodium-dependent calcium overload to treat myocardial ischemia.

Because intracellular sodium and calcium overload play a key role in both mechanical and electrical dysfunction during myocardial ischemia, inhibition of the late sodium current would be expected to decrease the intracellular sodium and calcium overloads and thereby reduce their undesirable effects. Ranolazine selectively inhibits late sodium current relative to peak sodium current, and attenuates the abnormalities of ventricular repolarization and contractility associated with ischemia. This is the currently proposed mechanism (hypothesis) of action of the effects of ranolazine during myocardial ischemia.

Effect of nifedipine on coronary hemodynamics in patients with left anterior descending coronary occlusion.

The mechanisms responsible for the beneficial effects of calcium channel antagonists in patients with effort angina were investigated by studying the coronary hemodynamic responses of the anterior left ventricular region before and after administration of nifedipine in 13 patients whose left anterior descending coronary artery was filled by flow from collateral vessels. Nifedipine was given bucally in a dose (10 or 20 mg) that decreased aortic pressure 5 mm Hg or more. Nifedipine increased collateral flow (regional thermodilution) in only three patients (p = NS), but consistently decreased coronary resistance in the left ventricular anterior region (p less than 0.05). Anterior region myocardial oxygen consumption did not change after nifedipine administration. Lactate metabolism was evaluated in eight patients: values were abnormal in four patients before nifedipine; after nifedipine, values remained abnormal in three of these patients and became abnormal in one other. During atrial pacing stress, angina occurred in all patients before nifedipine and at the same or lower heart rate in nine patients after nifedipine. After nifedipine administered at the same rate that induced angina during the control period, collateral flow and myocardial oxygen consumption were usually lower (both p less than 0.05), but anterior region coronary resistance was unchanged compared with control values. Lactate metabolism was not usually improved. Thus, although nifedipine maintained collateral flow while aortic pressure decreased, no consistent beneficial effect on pacing-induced angina was seen.

Regional coronary hemodynamic responses during the cold pressor test: lack of effect of nitroglycerin.

The effects of large coronary vessel dilation on responses to immersion of a hand and forearm in ice water for 1 minute (that is, the cold pressor test) were calculated for 17 patients. Regional coronary blood flow and aortic and left ventricular pressures were continuously measured before and during two cold pressor tests, each performed before and after administration of sublingual (0.4 mg) or low dose intracoronary (0.01 mg) nitroglycerin. During the initial cold pressor test, heart rate and coronary pressures increased in all patients; total and regional coronary resistance usually increased in patients with severe coronary artery disease and usually decreased in patients with a normal coronary angiogram. Sublingual nitroglycerin induced important systemic effects, but intracoronary nitroglycerin did not; both induced dilation of coronary arteries viewed angiographically. Regardless of the route of nitroglycerin administration, coronary hemodynamic responses were directionally similar during the repeat cold pressor test compared with the initial one. These data support the concept that changes in tone of the large coronary arteries are not important in producing the cardiac responses observed during the cold pressor test.

Laser recanalization of acutely thrombosed coronary arteries in live dogs: early results.

Laser recanalization was attempted in thrombosed coronary arteries of 10 dogs. In all dogs a coronary thrombus was obtained by passing a low grade electrical current through a guide wire advanced into the artery. Recanalization was then attempted using an argon laser with energy levels ranging from 3 to 30 J. In six dogs a 140 micron core optical fiber was positioned proximal to the thrombus and lasing was done during fiber advancement. The thrombosed artery was recanalized in one dog, perforated in four and neither recanalized nor perforated in one. In the remaining four dogs a steerable guide wire was advanced across the thrombus and a catheter was passed over the guide wire and exchanged for a 200 micron core optical fiber. After fiber withdrawal, mechanical recanalization without lasing was performed in one of the four dogs. In the remaining three dogs, both the fiber and the catheter were again advanced distal to the thrombus and lasing was done during withdrawal; this caused coronary perforation in all dogs. Laser recanalization of thrombosed coronary arteries in dogs using currently available techniques is feasible but results in a very high incidence of perforation.

Influence of acute aortic insufficiency on the hemodynamic importance of a coronary artery narrowing. II. Various magnitudes of aortic insufficiency.

Coronary hemodynamic effects of controlled acute aortic insufficiency were studied in 40 open chest dogs with and without graded coronary diameter narrowing. An adjustable basket device was used to regulate aortic insufficiency, creating three groups: group 1, mild to moderate aortic insufficiency (regurgitant fraction less than 50%); group 2, moderately severe aortic insufficiency (regurgitant fraction greater than 50%); and group 3, aortic insufficiency with mean aortic pressure restored to control levels. Mean coronary blood flow was similar to control values in group 1, but was higher in groups 2 and 3. The endocardial/epicardial flow ratio was similar with and without aortic insufficiency. With graded coronary narrowing greater than 80%, coronary flow and endocardial/epicardial flow ratio decreased with or without aortic insufficiency. However, endocardial/epicardial flow ratio usually decreased more during aortic insufficiency. Peak reactive hyperemic flow after release of a 10 second coronary occlusion also decreased during aortic insufficiency. The amount of decrease compared with control values was related to the magnitude of aortic insufficiency. This value with no coronary narrowing in group 1 was similar to peak reactive hyperemic flow with a 60% coronary narrowing during the control period. In group 2, peak reactive hyperemic flow was similar to that with an 80% coronary narrowing during the control period. Restoring mean aortic pressure to control values in group 3 did not restore peak reactive hyperemic flow to control values. These data suggest that coronary flow reserve assessed with coronary narrowings or during reactive hyperemia is decreased during aortic insufficiency. The decrease in coronary flow reserve was more pronounced as the magnitude of aortic insufficiency increased.

Regional coronary venous flow responses to transient coronary artery occlusion in human beings.

Coronary hemodynamic responses to transient coronary artery occlusion in 21 patients were investigated by using regional coronary venous thermodilution to measure regional coronary venous flows. Transient coronary artery occlusion was produced by coronary artery spasm (13 patients) or balloon inflation during coronary angioplasty (8 patients). The left anterior descending coronary artery was transiently occluded in 12 patients, the right coronary artery in 8 patients and the left circumflex artery in 1 patient. During transient coronary occlusion, regional venous flow decreased in 20 of the 21 patients (79 +/- 31 to 53 +/- 29 ml/min, mean +/- standard deviation [SD]; probability [p] less than 0.05) corresponding to the left ventricular region perfused by the occluded artery. Regional coronary resistance increased in all 21 of these regions (1.42 +/- 0.75 to 2.26 +/- 1.45 mm Hg/ml per min, p less than 0.05). Simultaneously measured blood flow and resistance in the left ventricular region supplied by the nonoccluded arteries did not change significantly (62 +/- 27 to 64 +/- 29 ml/min and 1.85 +/- 0.93 to 1.81 +/- 0.98 mm Hg/ml per min, respectively). Coronary hemodynamic changes were similar during transient coronary occlusion, whether produced by coronary spasm or by balloon inflation. However, the presence of angina, reversible electrocardiographic abnormalities and an increase of the left ventricular filling pressure were more common during coronary spasm (p less than 0.05 for all). Regional coronary hemodynamic changes during transient occlusion of the anterior descending, circumflex or right coronary artery were similar. These data show that coronary occlusion decreases regional left ventricular flow in the region perfused by the affected artery. The method of coronary occlusion or the coronary artery affected during occlusion did not seem to elicit different responses.

In vitro effects of argon laser radiation on blood: quantitative and morphologic analysis.

Use of the argon laser to recanalize stenosed arteries may require delivery of the beam through blood. To assess the degree of hemolysis and debris formation, 84 samples of citrated whole blood were exposed to argon laser radiation with varying power (1, 2 and 3 watts) and duration (5, 10, 20 and 40 seconds). Compared with control samples, only blood samples exposed to a power of 3 watts for 40 seconds showed a marked decrease in hematocrit (from 37 +/- 1.3 to 33 +/- 1.4%, p less than 0.01) and a marked increase in both free hemoglobin concentration (from 0.2 +/- 0.2 to 1.3 +/- 0.5 g/100 ml, p less than 0.01) and debris weight (from 0.9 +/- 0.3 to 2.8 +/- 0.5 mg, p less than 0.01). Scanning electron microscopy of debris from samples of whole blood, washed erythrocytes and platelet-rich plasma lased at 3 watts for 40 seconds documented the presence of membrane denaturation of blood elements, resulting in their fusion to form complex mesh-like conglomerates. Similar morphologic changes were observed in whole blood samples exposed to a "hot tip" rather than laser radiation. These data indicate that: 1) argon laser radiation with a power of 3 watts does not produce apparent hemolysis or debris formation for exposure periods up to 20 seconds, and 2) the effects of laser radiation on blood are probably mediated by thermal denaturation of cell membranes, as suggested by the same morphologic changes produced by thermal injury from a "hot tip."

Reduction in blood flow in normal and narrowed coronary arteries of dogs by leukotriene C4.

The hemodynamic effects of intracoronary leukotriene C4 (0.3 to 10.0 micrograms) in seven anesthetized dogs with normal and severely narrowed coronary arteries were examined. Intracoronary leukotriene C4 caused a significant dose-related reduction in coronary blood flow in both normal and narrowed coronary arteries with no effect on heart rate or mean arterial pressure. However, left ventricular end-diastolic pressure increased at the 10.0 micrograms dose. The reduction of blood flow in normal and narrowed coronary arteries in response to leukotriene C4 was similar. At the peak effects of leukotriene C4, there was evidence of intracoronary thromboxane A2 release. To examine the contribution of thromboxane A2 release to the coronary vasoconstrictor effects of leukotriene C4, dogs were administered leukotriene C4 after indomethacin pretreatment. The decrease in coronary blood flow was not significantly affected by pretreatment of the animals with indomethacin. However, indomethacin lowered baseline levels of thromboxane B2 and blocked the release of thromboxane A2 after leukotriene C4 administration. Thus, intracoronary leukotriene C4 causes direct dose-dependent decrease in coronary blood flow of similar magnitude in both normal and narrowed coronary arteries. These coronary hemodynamic effects of leukotriene C4 in dogs are not mediated by release of thromboxane A2. Leukotriene C4 released from activated leukocyte in the intracoronary thrombus or in the injured myocardium may reduce coronary blood flow and adversely influence the fate of the affected myocardial tissue.

Laser angioplasty with angioscopic guidance in humans.

An experimental study was conducted in 11 patients to evaluate the immediate effects of laser recanalization during peripheral arterial bypass surgery. Angioscopy allowed precise localization and identification of the occlusion. A 1 or 2 mm optical fiber probe was used. Laser energy was regulated using the least amount of energy necessary for recanalization. New vascular channels were made in 10 of the 11 patients. After recanalization the arterial segment was excised for histologic evaluation. Smaller channel diameters were made with the 1 mm probe (1.5 +/- 0.6 mm) than with the 2 mm probe (3 +/- 0.3 mm) (p less than 0.05). Flow through channels (mean pressure 80 mm Hg) made with the 2 mm probe was greater than that through channels made with the 1 mm probe (150 +/- 102 versus 19.7 +/- 10 cc/min) (p less than 0.05). The amount of debris formed was small with both probes. Vascular perforations were less frequent with the 2 mm probe (two of nine arteries) compared with the 1 mm probe (four of four arteries). Successful recanalization with flow rates expected to maintain vascular patency was achieved only with the 2 mm probe. Histologic studies at nonperforated sites demonstrated that the elastica of the artery appeared to be preserved whereas the overlying plaque and underlying media were thermally disrupted. This suggests that the elastic tissue acts as an optical window allowing the argon beam to go through it without causing morphologic damage. Except for fresh thrombus, atheromas including calcific plaque and old organized thrombus were readily vaporized. These results are encouraging for the use of the laser for vascular recanalization in humans.

Relation between clinical, angiographic and ischemic findings at baseline and ischemia-related adverse outcomes at 1 year in the Asymptomatic Cardiac Ischemia Pilot study. ACIP Study Group.

OBJECTIVES: We attempted to investigate the relation between patient characteristics and adverse outcome in patients with ischemia and clinically stable coronary artery disease (CAD). BACKGROUND: Evidence suggests that cardiac ischemia, detected by exercise stress testing (ETT) and ambulatory electrocardiographic (AECG) monitoring during daily living, identifies a subgroup of patients at increased risk for adverse outcome, but the relation between these ischemia findings and clinical and angiographic characteristics is largely unknown. METHODS: We examined the relation between clinical, angiographic and ischemia characteristics at entry with adverse outcome observed at 1 year in the 558 patients enrolled in the Asymptomatic Cardiac Ischemia Pilot (ACIP) study. RESULTS: By the 12-month visit 13.1% of patients had an ischemia-related adverse clinical outcome that included death, nonfatal myocardial infarction or an ischemia-related hospital admission. Multivariate analysis identified only the number of AECG ischemic episodes at entry (odds ratio [OR] 1.06, 99% confidence interval [CI] 1.01 to 1.12, p = 0.002) as an independent predictor of outcome. Assignment to revascularization (as opposed to an initial medical treatment strategy) showed a trend (OR 0.56, 99% CI 0.26 to 1.2, p = 0.05). None of the other baseline clinical, exercise or angiographic variables examined provided additional information relative to adverse outcome. CONCLUSIONS: Determinants of adverse outcome, among clinically stable patients with CAD and ischemia induced by stress and daily life were magnitude of AECG ischemia before treatment and, possibly, initial treatment assignment. Among the many other characteristics examined, including age, symptom status and angiographic and exercise variables, none contributed additional independent prognostic information. These two simple variables, which may be modifiable, need further study in a larger trial.

A detailed angiographic analysis of patients with ambulatory electrocardiographic ischemia: results from the Asymptomatic Cardiac Ischemia Pilot (ACIP) study angiographic core laboratory.

OBJECTIVES: The purpose of this Asymptomatic Cardiac Ischemia Pilot (ACIP) data bank study was to characterize angiographic features of coronary pathology of patients enrolled in the ACIP study. BACKGROUND: Ischemia during ambulatory electrocardiographic (AECG) monitoring is associated with increased morbidity and mortality. Reports relating AECG ischemia to severity or complexity of coronary artery disease are few in number and small in size and have produced conflicting results. METHODS: Coronary angiograms from patients with asymptomatic AECG ischemia enrolled in the ACIP study were reviewed at a central core laboratory. Quantitative measurement of percent stenosis and Thrombolysis in Myocardial Infarction flow grades were used to assess the severity of coronary artery disease. Lesions were also evaluated for the presence of intracoronary thrombus, ulceration and lumen contour as indicators of stenosis complexity. In addition, comparisons were made with 27 patients screened for the ACIP study, but who were found ineligible because they did not have AECG ischemia on 48-h Holter monitoring. RESULTS: A total of 329 (75%) of 439 patients with AECG ischemia had multivessel coronary artery disease. Proximal stenoses > or = 50% diameter reduction were common in patients with AECG ischemia (62.2%), as were proximal stenoses > or = 70% (38.7%). Features suggesting complex plaque were found in 50.1% of patients with AECG ischemia. CONCLUSIONS: Multivessel coronary artery disease, severe proximal stenoses and features of complex plaque were observed frequently in patients who exhibited AECG ischemia. The presence of severe and complex coronary artery disease may explain, in part, the increased risk for adverse outcome associated with ischemia during activities of daily life.

Asymptomatic Cardiac Ischemia Pilot (ACIP) study: impact of anti-ischemia therapy on 12-week rest electrocardiogram and exercise test outcomes. The ACIP Investigators.

OBJECTIVES: This report from the Asymptomatic Cardiac Ischemia Pilot (ACIP) study examines differences in the magnitude of reduction of myocardial ischemia as determined by exercise treadmill testing in patients randomized to three different treatment strategies: angina-guided medical therapy, ischemia-guided medical therapy and coronary revascularization. BACKGROUND: No prospective randomized clinical trials in patients with exercise electrocardiographic (ECG) abnormalities and asymptomatic cardiac ischemia on ambulatory ECG monitoring have compared the impact of different treatment strategies, including coronary revascularization, in terms of reducing myocardial ischemia. METHODS: The ACIP exercise protocol was used. Exercise variables measured included final exercise stage; presence of exercise-induced angina or ischemia; time to angina; time to 1-mm ST segment depression; number of exercise ECG leads with abnormalities; maximal depth of ST segment depression in any lead; sum of ST segment depression; ST/HR index; and rate-pressure product at time to angina, at time to 1-mm ST segment depression and at peak exertion. RESULTS: Peak exercise time was increased by 0.5, 0.7 and 1.6 min in patients assigned to the angina-guided, ischemia-guided and coronary revascularization strategies, respectively, from the qualifying visit to the 12-week visit (p < 0.001). At the qualifying visit, the sum of exercise-induced ST segment depression was 9.4 +/- 5.0 (mean +/- SD), 9.6 +/- 4.7 and 9.9 +/- 5.5 mm (p = NS) in the three treatment strategies, respectively. At the 12-week visit, the sum of exercise-induced ST segment depression was 7.4 +/- 5.7, 6.8 +/- 5.3 and 5.6 +/- 5.6 mm (p = 0.02) in the three treatment strategies, respectively. Each treatment strategy resulted in a significant reduction in all exercise-induced variables of myocardial ischemia measured at 12 weeks. CONCLUSIONS: Coronary revascularization significantly reduced the extent and frequency of exercise-induced myocardial ischemia compared with either medical strategy. The prognostic impact of these observations should be evaluated in a large-scale multicenter clinical trial.

Percutaneous left ventricular catheterisation with an ultraminiature catheter-tip pressure transducer.

Percutaneous left ventricular catheterisation with a 4F (O.D. 1.33 mm) catheter-tip pressure transducer is described. The transducer is small enough so that it can be introduced through a short 4F arterial insertion sheath or a Brockenbrough Trans-septal catheter. Experience in 35 patients suggests that this ultraminiature catheter mounted pressure transducer is a valuable addition to the cardiac catheterisation laboratory.

Transient S-T segment elevation in unstable angina: prognostic significance.

The clinical and prognostic significance of the direction of the S-T segment shift on the 12-lead electrocardiogram was evaluated in medically treated patients with unstable angina pectoris. Long-term mortality and morbidity of 11 patients with transient S-T segment elevation (group I) were compared to that of 21 patients with transient S-T segment depression (group II). The average follow-up duration was 62 months. There was no significant difference between groups I and II with respect to survival or nonfatal myocardial infarction over a five-year period. Mortality was related to the extent of coronary artery disease and left venticular ejection fraction rather than to the direction of the S-T segment shift.

Effect of glyceryl trinitrate on coronary and systemic hemodynamics in man.

The effects of sublingual and intracoronary nitrates on coronary artery diameter were evaluated in five separate experiments in man. The first three are concerned with sublingual nitrates and the last two with intracoronary nitrates. The data obtained indicate that (1) administration of a fixed dose sublingual nitrate results in an increase in percent coronary artery stenosis compared with control measurements; (2) small doses of sublingual nitrates can dilate coronary arteries without a significant reduction in systemic arterial pressure or increase in heart rate; (3) the magnitude of percent coronary artery dilation after a fixed dose of sublingual nitrate is inversely related to the size of the coronary artery, that is, the smaller the coronary artery diameter the greater the relative dilation after administration of sublingual nitrate; (4) fixed dose sublingual nitrate often dilated coronary stenoses, but the more narrow stenoses were less likely to dilate; (5) the optimal dose of intracoronary nitrate required to produce maximal or near maximal coronary dilation without clinically important systemic hemodynamic effects is in the range of 200 micrograms; (6) intracoronary nitrate is a more potent coronary artery dilator than sublingual nifedipine, when administered as a 10 mg dose.

Short-term efficacy of oral verapamil in rest angina. A double-blind placebo controlled trial in CCU patients.

To determine the efficacy and safety of oral verapamil in patients with rest angina admitted to the Coronary Care Unit (CCU), a double-blind placebo-controlled trial was undertaken. Of the 65 patients with rest angina screened for the study, 15 met the inclusion criteria (at least two episodes of chest pain associated with ST-T segment changes per 24 hours) during single-blind placebo phase (Day 1). Patients were then randomized to receive either placebo or verapamil (80 mg every 6 hours) on Day 2. Protocol was designed such that those who did not respond to the placebo (nonresponders) received verapamil, 80 mg every 6 hours, whereas verapamil nonresponders received increased doses (120 mg every 6 hours) on Day 3. Those who did respond (responders) continued to receive their medication. Similar action was taken on Day 4, depending on chest pain frequency and clinical evaluation. The study drug was unblinded on Day 4. At the end of the four-day period, 13 patients were receiving verapamil (nine patients, 80 mg every 6 hours, and four patients, 120 mg every 6 hours) and all but one were responders. One patient received placebo all through the period of the study and was also considered to be a responder. In the remaining one patient evidence of myocardial necrosis developed after he received a single dose of verapamil (80 mg on Day 2). Except for the prolongation of PR interval in two patients while taking verapamil, no side effects from verapamil therapy were observed. These data demonstrate the efficacy of oral verapamil in reducing episodes of myocardial ischemia in the majority of all patients with rest angina.

Use of nitrates in unstable angina pectoris.

The rationale for using intravenous nitrates in patients hospitalized with severe angina pectoris is that physiologic action is almost immediate. Many studies and clinical experience indicate that the use of this preparation results in a marked diminution of recurrent angina episodes in most patients. If adverse reactions such as severe hypotension or bradycardia occur, decreasing the dose or stopping it entirely corrects the problem. Intravenous nitroglycerin can be used in combination with other known antianginal agents, such as beta blockers and calcium antagonists. In clinical practice most patients are treated with nitrates and beta blockers or calcium antagonists because the combination of drugs may reduce ischemia and symptoms more than each drug used alone over a long period.