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1 The haemodynamic effects of labetalol 50 mg intravenously were studied in 13 hypertensive patients at rest in the supine and upright positions and during exercise using percutaneous right heart and brachial artery catheterization. 2 Labetalol induced immediate significant reductions in systolic and diastolic blood pressures in all conditions. 3 Heart rate, stroke volume and cardiac output were not significantly altered in the supine position at rest but were significantly reduced in the upright position. In addition systemic vascular resistance was significantly reduced. 4 During exercise, heart-rate, cardiac output and vascular resistance were significantly reduced; stroke volume was increased. Left ventriclac filling pressures were unchanged both at rest and during exercise. 5 It was concluded that these changes resulted from blockade to both alpha- and beta-adrenoreceptor.
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PMID:Haemodynamic effects of combined alpha- and beta-adrenoreceptor blockade after intravenous labetalol in hypertensive patients at rest and during exercise. 1 Sep 50

1 The circulatory effects of labetalol 25 mg intravenously in six patients during 1% halothane anaesthesia were studied. 2Labetalol caused a marked decrease in arterial pressure and a consistent but modest (20%) decrease in cardiac output. Heart rate was slowed and stroke volume did not change significantly. Central venous pressure increased and peripheral resistance decreased. 3 Increasing the halothane concentration of 3% led to marked myocardial depression as evidenced by reduced cardiac output and increased central venous pressure with increasing arterial hypotension. 4 Labetalol may be a suitable drug for controlling induced hypotension under general anaesthesia, although high concentrations of halothane should be used with care.
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PMID:Cardiovascular effects of labetalol during halothane anaesthesia. 99 Jan 59

The interaction of cocaine with myocardial and vascular adrenoceptors is incompletely understood. The systemic and coronary hemodynamic effects of intravenous cocaine (1.5 mg/kg) were examined in dogs with and without pretreatment with propranolol (2 mg/kg i.v.) or labetalol (5 mg/kg i.v.) on different days. A total of 24 experiments was completed (three sets of experiments) using eight dogs chronically instrumented for measurement of aortic and left-ventricular pressure, left-ventricular dP/dt, subendocardial segment length, coronary blood flow, and cardiac output. Myocardial oxygen consumption was estimated from the pressure work index (PWI). Cocaine significantly (p < 0.05) increased heart rate (+51 +/- 17 bpm), mean arterial pressure (+72 +/- 10 mm Hg), left-ventricular systolic and end-diastolic pressures (+56 +/- 9 and +14 +/- 6 mm Hg, respectively), coronary blood flow (+32 +/- 10 ml/min) and the PWI (+10.0 +/- 2.3 ml O2/min/100 g). Significant reductions in stroke volume (-9 +/- 5 ml) and percent segment shortening (-7.1 +/- 1.7) were observed. These changes returned to control after 30 min. After pretreatment with propranolol, the cocaine-mediated increases in mean arterial pressure, left-ventricular systolic pressure, rate-pressure product, and the pressure work index (4.4 +/- 0.7 ml O2/min/100 g) were significantly (p < 0.05) less than those observed with cocaine alone. Cocaine also reduced contractility [dP/dt50 (-341 +/- 80 mm Hg/s)] and increased systemic vascular resistance (+2703 +/- 339 dyn.s.cm-5) in the presence of propranolol. Labetalol abolished the cocaine-mediated increases in heart rate and coronary blood flow and significantly attenuated the increases in mean arterial pressure, left-ventricular systolic pressure, cardiac output, rate-pressure product, and calculated myocardial oxygen consumption when compared to results obtained with cocaine alone. The results demonstrate that a portion of the basic dynamic effects of cocaine is mediated by stimulation of alpha and beta adrenoceptors. Combined alpha and beta adrenergic blockade reduces the hemodynamic effects of cocaine more than beta blockade alone. During antagonism of the sympathomimetic response of cocaine, direct negative inotropic actions of this drug are unmasked.
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PMID:Attenuation of the systemic and coronary hemodynamic effects of cocaine in conscious dogs: propranolol versus labetalol. 133 1

The incidence of both systolic and diastolic hypertension is increased in elderly patients, therefore antihypertensive drugs are commonly used in this population. In addition to changes in blood pressure, the aging process also causes numerous changes in other physiological parameters, resulting in altered pharmacokinetic and pharmacodynamic responses to the drugs. The dosage regimens for thiazide diuretics and amiloride must be individually titrated in the elderly patient, since the elimination of these agents decreases concurrently with decreased renal function, as indicated by compromised creatinine clearance. The initial doses of the calcium antagonists should be decreased in elderly patients, since representative compounds from all 3 chemically heterogeneous classes have been shown to have decreased clearance in these patients which appears to be primarily due to the status of hepatic function in the patient. However, with verapamil, the dosage should be further decreased in association with compromised renal function. The dosage of the angiotensin converting enzyme (ACE) inhibitors should be adjusted according to renal function rather than age. Lisinopril, which is primarily eliminated unchanged, is usually given in lower doses in the elderly, and doses of both captopril and enalapril may need to be reduced, depending on renal function. While there is no need to adjust the dosage regimen for the alpha-adrenoceptor blocking drugs (prazosin, terazosin), caution should be used with the beta-adrenergic blockers, particularly the hydrophilic agents, since they are renally eliminated. Labetalol may be a suitable alternative beta-blocker for the elderly patient, since its pharmacodynamic properties of decreased systemic vascular resistance without changes in heart rate or stroke volume are preferential for the elderly patient, and its pharmacokinetics are relatively unchanged in this population. Drugs that act primarily through the central nervous system, such as clonidine, methyldopa and guanfacine, require smaller doses in the presence of renal dysfunction. In contrast, guanabenz is metabolised primarily by the liver, so it would appear to be useful in elderly patients with renal dysfunction despite the lack of studies in this population. Guanadrel, an adrenergic neuron blocking drug, also requires a dosage reduction in patients with impaired renal function. In addition to the pharmacokinetic changes that occur in the elderly patient, pharmacodynamic changes may also be anticipated due to receptor modifications. Older patients have a decrease in beta-receptor sensitivity, while alpha-receptor sensitivity does not change. When designing the dosage regimen for a senior patient with hypertension, the combination of all these variables must be considered.
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PMID:Antihypertensive therapy in the aged patient. Clinical pharmacokinetic considerations. 168 70

The cardinal hemodynamic disturbance in established essential hypertension is an increased total peripheral resistance. Monotherapy with conventional beta-blockers lowers blood pressure usually without any significant fall in total peripheral resistance. Generally, cardiac output is reduced at rest as well as during exercise. In recent years, beta-blockers with vasodilating activity have been developed. Labetalol induces nonselective beta-blockade and in addition reduction in vascular resistance mainly through alpha-blockade. Long-term hemodynamic data indicate gradual normalization of cardiac output, stroke volume, and total peripheral resistance--possibly due to regression of structural changes in the left ventricle and in the arterioles. Prizidilol is a nonselective beta-blocker with a direct vasodilator effect. One year results showed a very marked fall in blood pressure and total peripheral resistance and dramatic increase in posttreatment exercise stroke volume. Cardiac output was unchanged in spite of a reduction in heart rate. Due to side effects, the drug has been withdrawn. Dilevalol, which is the R-R' isomer of labetalol, is also a nonselective beta-blocker, but its vasodilating activity seems to be mainly due to partial beta 2-agonist activity. Preliminary data indicate a reduction in blood pressure--mainly due to a fall in total peripheral resistance. Studies in elderly patients or in patients with reduced left ventricular function seem to indicate that the drug might be used without deterioration of the heart pump function. Although antihypertensive properties of dilevalol have been extensively studied and are defined, the exact position of dilevalol among antihypertensive drugs will be more precisely determined in future studies.
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PMID:Hemodynamic effects of beta-blocking compounds possessing vasodilating activity: a review of labetalol, prizidilol, and dilevalol. 246 93

Hemodynamic data were analyzed from 25 courses of intravenous pulse labetalol therapy for postoperative hypertension in 12 patients after major vascular surgeries. The hemodynamic determinations were obtained an average of 15 minutes after a therapeutic total dose of 10-120 mg of labetalol (mean, 37.5 mg). The mean arterial pressure (MAP) decreased an average of 27 mmHg or 20% after intravenous labetalol. This normalization of the postoperative hypertension was associated with a 19% increase in cardiac output (CO) and cardiac index (CI) (CO mean increase of 0.58 L/min and CI increase of 0.31 L/min/m2). Commensurate with this decrease in MAP and increase in CO was an average decrease in systemic vascular resistance (SVR) of 625 dyne/sec/cm-5 or 25%. The pulmonary vascular resistance decreased 15 dyne/sec/cm-5 or 4%. The heart rate decreased 9 beats per minute or 10% and the left ventricular stroke work improved by 9% or 1.6 g/m2/beat while the right ventricular stroke work increased by 33% or 2.8 g/m2/beat. The hemodynamic responses to intravenous labetalol in these patients were all beneficial, and there were no adverse effects secondary to the pulse doses of labetalol. Labetalol appears to be safe and efficacious for the treatment of postoperative hypertension in patients undergoing major vascular surgery.
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PMID:The hemodynamic effects of intravenous labetalol for postoperative hypertension. 273 25

Labetalol (L) was intravenously given to ten patients with an acute elevation of arterial blood pressure above to 200 to 100 mmHg. Blood pressure was controlled in 9 of 10 patients (less than or equal to 170/100 mmHg) with 50 mg in 4, 100 mg in 4 and 200 mg L in 1 patient. In 9 responders, systolic pressure decreased from 207 +/- 20 to 161 +/- 9, diastolic pressure from 107 +/- 11 to 90 +/- 8, and mean pressure from 140 +/- 11 to 113 +/- 5 mmHg, and all pressures remained at these levels during a 25 min control period. Heart rate decreased significantly from 87 +/- 20 to 69 +/- 11 per min and cardiac index from 3.2 +/- 0.8 to 2.6 +/- 0.61/min x m2. Stroke volume index remained unchanged. Total peripheral resistance and pulmonary artery occlusion pressure were not significantly altered but tended to increase, resulting in a small shift to the right of the ventricular function curve. Pulmonary vascular resistance increased significantly from 236 +/- 108 to 314 +/- 132 dyn x sec x cm-5 and mixed venous oxygen saturation decreased from 70 +/- 5 to 65 +/- 8%. Peripheral resistance was considerably higher and cardiac index lower in patients with a heart rate below 70/min. We conclude that L effectively lowers the arterial blood pressure in hypertensive crisis, but the substance should not be used in patients with heart rates below 70/min, as in this case the beta-blocking effect may supervene resulting in a high-resistance low-output state.
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PMID:[Effectiveness and hemodynamic mechanism of action of blood pressure lowering by intravenous labetalol in patients with a critical increase in blood pressure]. 277 Jan 85

Labetalol is a unique antihypertensive agent which is a competitive peripheral antagonist at both alpha- and beta-adrenoceptor sites. Clinically, it possesses about one fourth of the beta-adrenoceptor blocking activity of propranolol and one half of the alpha-adrenoceptor blocking activity of phentolamine with a beta- to alpha-blocking ratio of approximately 7:1. Nowadays, the clinical profile of labetalol is clearly defined. Perorally, it has often been used in the treatment of mild, moderate and severe hypertension and intravenously in the management of hypertensive emergencies. It offers many advantages over beta-blockers with no prominent side-effects. Hemodynamically, labetalol reduces blood pressure, heart rate and, first of all, peripheral resistance with almost no change in resting cardiac output or stroke volume. Labetalol appears to be useful particularly in patients whose blood pressure is not adequately controlled by beta-blockers alone or combined with a diuretic, but sometimes at the expense of postural hypotensive side-effects. It has proved to be safe in patients with coronary artery disease or after acute myocardial infarction and in pregnant patients, but in phaechromocytoma further clinical experience is needed. In induced hypotension during anesthesia and surgery no invasive blood pressure measurements are needed. The most frequent adverse effects include fatigue, postural hypotension, headache and gastrointestinal complaints. On the whole, labetalol expands the armamentarium of the practising physician in the treatment of hypertension of different origin.
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PMID:Current status of labetalol, the first alpha- and beta-blocking agent. 286 49

The haemodynamic impact of alpha- and beta-adrenoceptor blockade (labetalol) was compared with that of slow-calcium channel blockade (nifedipine) in 32 patients with sustained elevation of systemic arterial pressure (systolic blood pressure greater than 160; diastolic blood pressure greater than 95 mmHg) following a recent myocardial infarction (6-22 h). Patients with normal (pulmonary artery occluded pressure; (PAOP less than 18 mmHg; n = 16) or impaired (PAOP greater than 18 mmHg; n = 16) left ventricular function were randomized to labetalol (1 mg/kg i.v. 15 min) or nifedipine (20 mg sublingually) and haemodynamic profile was measured over 2 h. Both drugs equally reduced mean systemic arterial pressure (P less than 0.01 versus pretreatment control), and presumably left ventricular afterload; however, the heart rate (P less than 0.01) and cardiac index (P less than 0.01) increased after nifedipine, contrasting with reductions in both variables following labetalol (P less than 0.01). The elevated left ventricular filling pressure was reduced by both labetalol (P less than 0.05) and nifedipine (P less than 0.01) but the reduction was greater following nifedipine (-2 mmHg versus -5 mmHg, P less than 0.05). Thus both compounds were equally effective hypotensive agents. Labetalol consistently reduced cardiac stroke work and double product, important determinants of myocardial oxygen requirements; however, nifedipine afforded some improvement in cardiac performance in patients with left ventricular dysfunction.
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PMID:Sympathetic (alpha-beta) or calcium channel blockade for hypertensive myocardial infarction? A haemodynamic comparison of labetalol and nifedipine. 290 56

Twenty young (45 years or younger) and 20 older (55 years or older) adult patients with mild hypertension were enrolled in this study to compare the hemodynamic effects of labetalol versus placebo in two age groups. Ten patients in each group were randomly assigned to receive either a single oral dose of labetalol (200 mg) or placebo. Hemodynamic parameters were recorded immediately before and two hours after ingestion. Labetalol was more effective than placebo in significantly lowering systolic blood pressure (-11 versus + 5 mm Hg, -23 versus + 4 mm Hg), diastolic blood pressure (-9 versus + 2 mm Hg, -12 versus + 5 mm Hg), and total systemic resistance (-259 versus + 42 dynes-sec cm-5, -390 versus + 74 dynes-sec cm-5) in young and older hypertensive subjects, respectively. There was no significant changes in heart rate, stroke volume index, or cardiac index in either age group. These data indicate that labetalol lowers blood pressure in young an older hypertensives primarily by reducing peripheral resistance and that the antihypertensive effect may be somewhat greater in older patients.
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PMID:Hemodynamic effects of labetalol in young and older adult hypertensives. 339 30


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