Systemic and coronary hemodynamics of labetalol in normotensive patients with ischemic heart disease.

The systemic and coronary hemodynamic effects of combined alpha- and beta-adrenergic blockade produced by labetalol were assessed in 24 normotensive patients with angina pectoris and an ischemic electrocardiographic response to exercise stress. Both the intravenous (0.5 mg/kg) and oral (200 mg) formulations of labetalol were evaluated. At rest, labetalol produced systemic vasodilation (systemic vascular resistance -16% after intravenous and -8% after oral labetalol, both p less than 0.05) without change in heart rate. Aortic pressure usually was lower and cardiac output preserved or increased. Left ventricular end-diastolic pressure was unchanged. Coronary sinus flow was usually unchanged after either route of administration. Exercise duration was prolonged in 14 of the 20 patients with severe coronary artery disease. During exercise, tachycardia was blunted (-12% after intravenous, -7% after oral labetalol, both p less than 0.05) as was the increase in mean aortic pressure (-12% and -13% intravenous and oral labetalol respectively, both p less than 0.05), left ventricular end-diastolic pressure [-7% and -1%, respectively, both p = not significant (NS)] was unchanged. Coronary sinus flow (-16% and -25%, respectively, both p less than 0.05) was decreased as heart rate and aortic pressure were lower. Cardiac output, systemic vascular resistance, and coronary vascular resistance were similar to control exercise. The hemodynamic effects of intravenous and oral labetalol are, in general, similar. Hemodynamic responses differ from those produced by other beta-blockers and by calcium antagonists.

Systemic and coronary hemodynamic effects of combined oral alpha- and beta-adrenergic blockade (labetalol) in normotensive patients with stable angina pectoris and positive exercise stress tests.

The systemic and coronary hemodynamic effects of combined alpha- and beta-adrenergic blockade produced by oral labetalol were assessed in 12 normotensive patients with angina pectoris and an ischemic electrocardiographic response to exercise stress. At rest, labetalol (200 mg, orally) produced systemic vasodilation (systemic vascular resistance -9%, p less than .01) as aortic pressure fell and cardiac output was unchanged. Left ventricular (LV) end-diastolic pressure also fell slightly (17%, p = .05). Systemic vasodilation was not accompanied by reflexly mediated increases in heart rate. Coronary flow and resistance and myocardial oxygen uptake were unchanged. Before labetalol, supine bicycle exercise produced angina in 10 patients. After labetalol, exercise duration was prolonged in 6 of these 10 (average 56%). During exercise, tachycardia was blunted (-7%, p less than .05) as were increases in aortic pressure (-12%, p less than .01) and coronary sinus flow (-25%, p = .03). Cardiac output and LV end-diastolic pressure were similar to control period values. These hemodynamic effects of oral labetalol appeared beneficial, differed from those expected of classic beta-adrenergic blocking agents, and were, in general, similar to those we have observed after intravenous labetalol. The clinical response was good and the drug safe. Labetalol should undergo further evaluation in normotensive as well as hypertensive patients with ischemic heart disease.

Comparison of selective (beta 1) and nonselective (beta 1 and beta 2) beta-adrenergic blockade on systemic and coronary hemodynamic findings in angina pectoris.

To investigate the influence of selective beta 1-adrenergic blockade, in contrast to beta 1- and beta 2-adrenergic blockade, systemic and coronary hemodynamics were studied. Measurements were made at rest and during exercise in 23 patients with suspected coronary artery disease (CAD) before and after either metoprolol or propranolol, given in doses to provide comparable beta 1-receptor blockade. Quantitative coronary angiography was performed at rest. Using a randomized, double-blind protocol, either beta 1 and beta 2 blockade was produced by propranolol (0.1 mg/kg intravenously), or selective beta 1 blockade was produced by metoprolol (0.15 mg/kg intravenously). As expected, at these doses both drugs produced a comparable decrease in heart rate at rest and during exercise, averaging 9% and 14% after propranolol and 10% and 16% after metoprolol. Exercise duration to ischemia was prolonged in most patients with severe CAD after either propranolol (5 of 7) or metoprolol (6 of 10) treatment. The effects of these 2 beta-blocking drugs on systemic hemodynamic values at rest and during exercise were similar. Additionally, coronary sinus flow was usually unchanged by both drugs at rest (-5% after propranolol and -4% after metoprolol, differences not significant) and decreased a similar amount during exercise (-15% after propranolol and -9% after metoprolol, both p less than 0.05). Coronary resistance did not change significantly with either drug (0% after propranolol and 3% after metoprolol), and during exercise (11% after propranolol and 3% after metoprolol), suggesting that decreases in flow were secondary to reduced demand. Furthermore, neither drug produced detectable changes in coronary artery size.(ABSTRACT TRUNCATED AT 250 WORDS)

Fatal hydrofluoric acid cutaneous exposure with refractory ventricular fibrillation.

A patient with hydrofluoric acid burns involving only 8% of his body surface area died from intractable cardiac arrhythmia secondary to the depletion of ionized calcium by fluoride ion. For burns of this type, immediate subcutaneous injection of 10% calcium gluconate into the burn wound is recommended and the dose given should be titrated to the relief of local pain. Immediate debridgement of the burn wound also can decrease the treacherous aspect of the circulating fluoride ion, which binds to calcium to form an insoluble salt, effectively removing the calcium ion from any physiologic interaction.

Systemic and coronary hemodynamic effects of combined alpha- and beta-adrenergic blockade (labetalol) in normotensive patients with stable angina pectoris and positive exercise stress test responses.

The systemic and coronary hemodynamic effects of combined alpha- and beta-adrenergic blockade produced by labetalol were assessed in 12 normotensive patients with angina pectoris and an ischemic electrocardiographic response to exercise stress. When given to the patient at rest, labetalol (0.5 mg/kg intravenously) produced systemic and coronary vasodilation (mean 16% and 13%, respectively, both p less than 0.05); aortic pressure decreased, cardiac output increased and coronary flow and heart rate did not change. Before labetalol treatment, supine bicycle exercise produced angina in all patients. After treatment, exercise duration was prolonged in 8 patients (average 33%). At the same duration of exercise that led to angina during the control period, ST depression in lead V5 was less after labetalol (from 1.2 to 0.4 mm, p less than 0.5). During exercise, tachycardia was blunted (-12%, p less than 0.05) as were the increases in aortic pressure (-12%, p less than 0.05), left ventricular end-diastolic pressure (-7%, difference not significant) and coronary sinus flow (-16%, p less than 0.05). Cardiac output and systemic and coronary vascular resistance were similar to values during control exercise. The hemodynamic effects of labetalol appeared to be beneficial and differed from those of classic beta-adrenergic blocking agents.

Comparison of diltiazem and nifedipine alone and in combination in patients with coronary artery spasm.

Fifteen patients with coronary artery spasm completed a double-blind placebo-controlled trial comparing diltiazem and nifedipine. Increasingly, higher daily doses (diltiazem, 90 to 360 mg; nifedipine, 30 to 120 mg) were administered to achieve optimal clinical effects. Daily diaries and ambulatory electrocardiographic recordings were used to assess efficacy and side effects. Both drugs significantly decreased angina frequency compared with that in the preceding placebo period (diltiazem 1.4 +/- 0.4 [mean +/- SEM] to 0.4 +/- 0.2 episodes per day; nifedipine 1.4 +/- 0.3 to 0.4 +/- 0.1 episodes per day; both p less than 0.05). Ambulatory electrocardiographic recordings showed fewer ST shifts than were expected during all treatment periods (0.02/h recorded during placebo, none during diltiazem and 0.02/h during nifedipine therapy). Although some patients responded better to one drug than the other, neither drug resulted in a clearly superior clinical response. Diltiazem was discontinued in one patient because of urticaria, but the total number of side effects was higher with nifedipine (12 of 15 patients) than with diltiazem (5 of 15, p less than 0.01). Nine patients remained symptomatic on single drug treatment and entered open label treatment with the combination of diltiazem and nifedipine. Three patients did not tolerate the combination because of important side effects; the other six also had side effects, but these were relatively minor. Four patients received no more benefit from the combination than from a single agent; the condition of two patients improved. Both diltiazem and nifedipine provide effective antianginal therapy for coronary spasm, but diltiazem has fewer side effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Percutaneous transluminal coronary angioplasty in evolving acute myocardial infarction.

In 29 patients with evolving acute myocardial infarction, acute reperfusion of the infarct-related coronary artery was attempted using percutaneous transluminal coronary angioplasty (PTCA). Before PTCA, angiography showed 23 totally occluded and 6 severely stenotic infarct-related coronary arteries. PTCA was initially successful in 25 of 29 patients (86%). Reocclusion occurred in 4 patients within 12 hours after successful PTCA and was associated with new electrocardiographic changes or recurrence of symptoms. In 17 patients the infarct-related coronary artery remained patent at early follow-up; late stenosis occurred in 4 patients. Recurrence of stenosis was accompanied by development of angina. No clinical or angiographic features distinguished those with ultimate vessel patency, occlusion or recurrence of stenosis. On follow-up, ventricular function appeared better preserved or improved in those with a patent infarct-related coronary artery than in those with an occluded infarct-related coronary artery. Further studies are warranted to compare PTCA and streptokinase as primary reperfusion modalities in evolving acute myocardial infarction.

Combined hemodynamic effects of nifedipine and nitroglycerin in congestive heart failure.

To determine if the addition of preload reduction with nitrates would potentiate the acute vasodilator actions of nifedipine, we titered intravenous nitroglycerin in seven patients with severe congestive heart failure after they received a single oral dose of nifedipine. The peak hemodynamic effect of nifedipine occurred at 30 minutes, with large reductions of systemic vascular resistance (1831 +/- 128 to 1132 +/- 154 dynes X sec X cm-5; p less than 0.001) and mean arterial pressure (87 +/- 7 to 71 +/- 7 mm Hg; p less than 0.01). This was associated with an increase of stroke volume index from 22 +/- 3 to 27 +/- 3 ml/m2 (p less than 0.01) but no significant changes in heart rate, right atrial pressure, or pulmonary wedge pressure. These hemodynamic changes were attenuated over a 2-hour observation period. At 2 hours, the addition of intravenous nitroglycerin resulted in large reductions in right atrial pressure (9 +/- 2 to 6 +/- 1; p less than 0.01) and pulmonary wedge pressure (23 +/- 2 to 17 +/- 2; p less than 0.001). This was associated with further increases in cardiac index (from 1.99 +/- .15 to 2.25 +/- .14 L/min/m2; p less than 0.001) and stroke volume index (26 +/- 3 to 29 +/- 3 ml/m2; p less than 0.01). Thus, the addition of nitroglycerin to nifedipine will optimize preload reduction and enhance the vasodilator action of nifedipine. Further controlled studies are necessary to determine the long-term hemodynamic effects and the clinical role of nifedipine and its combination with nitrates in patients with severe congestive heart failure.

Immediate converting-enzyme inhibition with intravenous enalapril in chronic congestive heart failure.

To test the hypothesis that intravenous enalapril is a useful pharmacologic probe of the renin angiotensin system, intravenous enalapril was administered to 9 patients with severe congestive heart failure (CHF). This produced abrupt and complete blockade of converting enzyme, with peak effect occurring at 30 minutes, as reflected by increases of plasma renin activity (from 16.8 +/- 6 to 86.6 +/- 23 ng/ml/hour) and decreases of plasma aldosterone levels (from 46 +/- 14 to 25 +/- 6 ng%) (both p less than 0.05). With reduction of angiotensin II--mediated vasoconstriction, systemic vascular resistance decreased markedly (from 1,974 +/- 233 to 1,400 +/- 136 dyne s cm-5) and cardiac index was improved (from 1.88 +/- 0.9 to 2.20 +/- 0.21 liters/min/m2) (both p less than 0.05). The time course of angiotensin II levels suggested that the lack of a cumulative effect from additive doses of intravenous enalapril was a reflection of complete inhibition of converting enzyme. One patient did not respond to enalapril; despite comparable hemodynamic severity of CHF, the renin-angiotensin system was not activated in this patient. Thus, intravenous enalapril is capable of rapid and complete inhibition of converting enzyme for the accurate assessment of angiotensin II--mediated vasoconstriction in patients with severe CHF.

Evaluation of calcium-mediated vasoconstriction in chronic congestive heart failure.

Intercellular vascular smooth muscle calcium results in vasoconstriction and is therefore a potentially adverse mechanism of increased afterload in chronic congestive heart failure. Therefore, an evaluation was made of supine and tilt hemodynamic data, sympathetic reflexes, and the hormonal response to calcium channel antagonism after administration of nifedipine in nine patients with severe chronic congestive heart failure. After a 10 mg oral dose, the peak hemodynamic response occurred at 30 minutes and was characterized primarily by afterload reduction, improvement of systemic flow, and reduction of pulmonary hypertension. Despite reduction of supine blood pressure, there was no orthostatic hypotension during head-up tilt at the same time of peak response. Reflex responses to sympathetic stimulation (cold pressor test) were improved but still attenuated when compared with normal responses. Plasma renin activity increased significantly, but a dissociation of the aldosterone response was observed. Plasma catecholamine levels were not significantly altered. In summary, calcium antagonism resulted in significant afterload reduction and hemodynamic improvement in chronic congestive heart failure. This was associated with improved reflex responsiveness and, potentially, altered other vasoconstrictor hormones independently of the hemodynamic response. Calcium antagonism may provide a means to further understand vasoconstrictor mechanisms in heart failure and enhance therapy in appropriate patient subsets.

Profound bradycardia following release of cardiac tamponade. Hypothesis for reflex control.

A 58-year-old patient with chronic renal failure presented for routine hemodialysis, and was noted to have severe hypotension and findings on examination compatible with cardiac tamponade. The patient had emergency construction of a pericardial window. At the time of surgery, rapid evacuation of the pericardial space resulted in rebound hypertension associated with marked bradycardia. The features of the patient's case were analogous to the cardiovascular and reflex adjustments that normally occur during the Valsalva maneuver. These findings suggest that the cardiovascular changes occurring during the rapid decompression of cardiac tamponade may be reflexly-mediated, and gradually decompression of the pericardial space is therefore recommended to avoid reflex hypertension and bradycardia.