Total effective compliance, cardiac output and fluid volumes in essential hypertension

Total effective compliance, hemodynamic parameters, extracellular fluid volume, cardiopulmonary (CPBV) and total blood (TBV) volumes were determined in 32 men, including 14 normotensive controls and 18 sustained essential hypertensive patients. The effective compliance was calculated from the changes in central venous pressure recorded simultaneously with the changes in blood volume obtained after a rapid Dextran infusion. In normotensive controls, compliance was 2.08 +/- 0.09 ml/mm Hg/kg and was positively correlated with plasma (r = 0.79) and extracellular fluid (r = 0.84) volumes. In hypertensives, compliance was significantly reduced (1.49 +/- 0.06 ml/mm Hg/kg; P is less than 0.001) and was correlated negatively with the CPBV/TBV ratio (r = -0.75) and positively with the plasma volume/interstitial fluid volume ratio (r = 0.84). These results suggest that in normotensives, there is a regulatory mechanism between volume and compliance and that this contributes to maintaining filling pressure and cardiac output within normal ranges. In hypertensives, the reduced compliance could participate in the maintenance of normal values of cardiac output and extracellular fluid volume by influencing the partition of intravascular and extracellular fluid volumes.     

Vascular reactivity to norepinephrine and hemodynamic parameters in borderline hypertension

Pressor response to norepinephrine, cardiopulmonary blood volume, and hemodynamic parameters were studied in 41 borderline hypertensive patients in comparison with 42 permanent essential hypertensive patients and 28 normal subjects. Borderline hypertensive subjects had a high cardiac index (p < 0.0001), normal total peripheral resistance, and low total blood volume (p < 0.005). The ratio between cardiopulmonary blood volume (CPBV) and total blood volume (TBV) was significantly higher in comparison with normal subjects (p < 0.01) and permanent hypertensive subjects (p < 0.001). The pressor dose of norepinephrine was elevated (p < 0.0001) and was directly correlated with the basal values of the cardiac output (p < 0.005), the cardiopulmonary blood volume (p < 0.001), and the $\text{CPBV}\text{TBV}$ ratio (p < 0.01). None of these results was observed in permanent hypertensive subjects: the only significant result was a negative correlation between the pressor dose of norepinephrine and the basal diastolic arterial pressure (p < 0.0001). This study provides evidence that the cardiac output elevation in borderline hypertensive subjects was related to increased venous return and enhanced sympathetic venous tone.     

Hemodynamic effects of massive peripheral edema

The possibility that noncardiac massive peripheral edema reduces venous distensibility was investigated in eight patients in the supine and 80-degree head-up tilt position before and after diuretic therapy. After clearance of the edema with diuretic therapy, total blood volume (TBV) was not significantly decreased; therefore, in the supine position the significant (2p less than 0.001) decrease of right atrial pressure, stroke volume, cardiac output, and cardiopulmonary blood volume (CBV) by the diuretics was due to an improvement in venous compliance which resulted in peripheral redistribution of CBV since the ratio CBV/TBV was decreased during diuretic therapy (2p less than 0.001). Furthermore, before diuretic therapy, tilt significantly decreased right atrial pressure, stroke volume, cardiac output, CBV, and the ratio CBV/TBV; but after diuretic therapy, the decrease of the same variables during tilt was significantly (2p less than 0.001) greater. These results indicate that marked peripheral edema considerably decreases venous compliance which can be improved with diuretic therapy.     

Increased total vascular capacity in conscious cirrhotic rats.

The purpose of the present study was to determine the role of the systemic venous circulation in the hemodynamic alterations of the cirrhotic disease. Cardiac output (thermodilution; n = 8), mean circulatory filling pressure (balloon technique; n = 6), and blood volume (Evans blue dye; n = 7) were investigated in a rat model of liver cirrhosis without ascites induced by a 12-week individualized CCl4/phenobarbital treatment. Compared with control rats, conscious cirrhotic rats showed a hyperdynamic circulation characterized by normotension, high cardiac output (51 +/- 4.8 vs. 28.6 +/- 1.3 mL.min-1.100 g-1; P less than 0.01), and expanded blood volume (6.5 +/- 0.15 vs. 5.4 +/- 0.22 mL.100 g-1; P less than 0.05). There were no significant differences between control and cirrhotic rats in mean circulatory filling pressure (6.40 +/- 0.27 vs. 5.99 +/- 0.22 mm Hg, respectively) or in the pressure gradient for venous return (6.17 +/- 0.19 vs. 5.8 +/- 0.21 mm Hg, respectively). To further examine the venous tone, effective vascular compliance was estimated with the vascular filling-blood volume relationship by measuring the vascular filling before and after rapid changes in volume (+/- 8 mL.kg-1). Compliance was similar in both control and cirrhotic rats (3.15 +/- 0.26 and 3.41 +/- 0.21 mL.mm Hg-1), but the vascular filling-total blood volume relationship of the cirrhotic rats was displaced toward the volume axis. In conclusion, the increase in blood volume without changes in mean circulatory filling pressure (or venous tone) of the cirrhotic rats indicates a situation with venodilation and elevated total venous capacity; this is likely to be an important mechanism that could explain the hyperdynamic circulation of the cirrhotic disease.     

Development of tolerance to nitroglycerin in the arterial and venous circulation of dogs

The purpose of this study was to define the effects of nitroglycerin on venous tone and to investigate the time course of nitroglycerin tolerance in the peripheral circulation. The changes in the arterial and venous circulation resulting from an intravenous infusion of nitroglycerin (5 micrograms/kg per min) after 5 minutes (acute infusion) were compared with those changes that occurred after 2 hours (chronic infusion) of the same infusion in six splenectomized, ganglion-blocked dogs. Hemodynamics, blood volume and venous and arterial compliance were measured during each infusion. Nitroglycerin initially decreased mean arterial pressure from 81.5 +/- 2.0 to 57.6 +/- 2.7 mm Hg (p less than 0.01). Central blood volume decreased from 21.1 +/- 1.4 to 15.9 +/- 1.1 ml/kg (p less than 0.01), while total blood volume and unstressed vascular volume did not change. In the acute study, nitroglycerin increased venous compliance 33% from 1.75 +/- 0.14 to 2.32 +/- 0.16 ml/mm Hg per kg (p less than 0.01) and arterial compliance 33% from 0.049 +/- 0.007 to 0.065 +/- 0.007 ml/mm Hg per kg (p less than 0.01). At the end of the 2 hour infusion, arterial pressure increased and was now unchanged from control. Central blood volume had returned to baseline, 17.8 +/- 0.9 ml/kg. Total blood volume and unstressed vascular volume remained unchanged. With the long-term infusion, both arterial and venous compliance decreased (p less than 0.02) to 0.050 +/- 0.006 and 1.50 +/- 0.06 ml/mm Hg per kg, respectively, such that neither value was different from control. Nitroglycerin levels remained constant throughout.(ABSTRACT TRUNCATED AT 250 WORDS)     

Decrease in blood pressure and increase in total peripheral vascular resistance in supine resting subjects with normotension or essential hypertension

Hemodynamic changes in the supine resting position were investigated in 70 male subjects, consisting of 15 healthy volunteers with normotension (blood pressure of 113 +/- 7/70 +/- 5 mmHg, M +/- SD), 25 patients with borderline essential hypertension (143 +/- 12/90 +/- 6 mmHg) and 30 patients with established essential hypertension (166 +/- 13/108 +/- 6 mmHg). The supine position reduced blood pressure, heart rate, stroke volume and cardiac output (p less than 0.001), but increased total peripheral vascular resistance (p less than 0.001). The decrease in systolic blood pressure (p less than 0.01), stroke volume (p less than 0.05) and cardiac output (p less than 0.05), and the increase in total peripheral vascular resistance (p less than 0.01) were significantly greater in the borderline and established essential hypertensive groups than in the normotensive group. The results demonstrated that the decrease in blood pressure was due to a reduction in both heart rate and stroke volume, and that the decrease in stroke volume and increase in total peripheral vascular resistance seen in the supine position were greater in the hypertensive groups than in the normotensive group. These hyperresponses may contribute to the development and persistence of high blood pressure in patients with essential hypertension.     

Hemodynamic response to exercise after propranolol in patients with mitral stenosis.

Hemodynamic response to exercise before and 10 minutes after propranolol (5 mg intravenously) was studied in 10 young patients with pure mitral stenosis who had normal sinus rhythm and no cardiac failure. After propranolol the mean heart rate and cardiac index at rest were lower than during the control state (respectively, 95 +/- 4 versus 82 +/- 3 beats/min, P less than 0.005; 3.4 +/- 0.2 versus 2.8 +/- 0.1 liters/min per m2, P less than 0.025). As a result, the mean pulmonary wedge pressure and mean mitral valve gradient at rest were lower (respectively, 22 +/- 2 versus 18 +/- 2 mm Hg, P less than 0.005; 24 +/- 2 versus 17 +/- 2 mm Hg, P less than 0.001). During exercise after propranolol the values of pulmonary wedge pressure and mitral valve gradient were lower than control values during exercise (respectively, 39 +/- 3 versus 30 +/- 2 mm Hg, P less than 0.005; 44 +/- 3 versus 32 +/- 3 mm Hg, P less than 0.005), again because of the lower heart rate and cardiac index (130 +/- 6 versus 104 +/- 6 beats/min, P less than 0.001; 4.6 +/- 3 versus 3.7 +/- 2 liters/min per m2, P less than 0.01). Left ventricular end-diastolic pressure and stroke index showed no significant changes. Thus, propranolol may benefit patients with pure mitral stenosis with sinus rhythm and no cardiac failure whose symptoms occur during those reversible conditions characterized by an increase in heart rate or cardiac output, or both.     

Effects of alpha-adrenergic stimulation and beta-adrenergic blockade on azygos blood flow and splanchnic haemodynamics in patients with cirrhosis

The effects of beta-blockade with propranolol and of alpha-adrenergic stimulation with methoxamine, a powerful alpha-agonist, on azygos blood flow and on systemic and hepatic haemodynamics were investigated in 26 cirrhotic patients with portal hypertension. Beta-adrenergic blockade with propranolol (n = 12), evidenced by a significant reduction of heart rate (-17 +/- 1%, P less than 0.001) and cardiac index (-17 +/- 2%, P less than 0.001), caused a mild but significant decrease of hepatic venous pressure gradient (-10 +/- 2%, P less than 0.05) and a marked fall of azygos venous blood flow (-31 +/- 5%, P less than 0.05). Alpha-adrenergic stimulation with methoxamine (n = 14), manifested by a significant increase of mean arterial pressure (19 +/- 2%, P less than 0.001), mimicked the effects of propranolol on hepatic venous pressure gradient (-10 +/- 4%, P less than 0.05) and cardiac index (-11 +/- 2%, P less than 0.001). However, azygos blood flow was not significantly reduced by methoxamine (0.7 +/- 0.1 vs 0.6 +/- 0.1 l/min). On the contrary, hepatic blood flow was significantly reduced by methoxamine (-19 +/- 4%, P less than 0.01) but not by propranolol (-7 +/- 7%, ns). Similarly, in 8 patients who received methoxamine after being beta-blocked by propranolol, azygos blood flow, that was markedly reduced by beta-blockade, did not experience a further reduction but increased slightly by alpha-adrenergic stimulation, while hepatic blood flow, that was not reduced by propranolol, decreased significantly during the subsequent methoxamine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of nicardipine hydrochloride on circulating blood volume and vascular compliance in dogs

We studied the effect of nicardipine on the canine cardiovascular system, especially on total blood volume and vascular compliance. Under light halothane anesthesia, nicardipine decreased total blood volume significantly (from 80.0 +/- 8.4 ml/kg in the control state to 75.3 +/- 8.0 ml/kg under nicardipine administration, p less than 0.01), while it increased central circulating blood volume (from 17.1 +/- 5.9 ml/kg to 25.5 +/- 8.2 ml/kg, p less than 0.01), increased cardiac output and central venous pressure, and decreased mean arterial pressure (from 134.3 +/- 16.2 mmHg to 93.9 +/- 17.1 mmHg, p less than 0.01) and total peripheral resistance. Vascular compliance derived from fluid infusion experiments showed a significant decrease (from 8.9 +/- 3.8 ml/mmHg/kg to 5.5 +/- 8.0 ml/mmHg/kg, p less than 0.01). In addition to the vasodilatory action of nicardipine on arteries, these findings also suggest that 1) nicardipine causes a fluid shift from the vascular to the interstitial fluid space as a result of increased capillary pressure, 2) it increases preload through blood redistribution from the peripheral to the central circulation, and 3) it decreases compliance of the vessels, perhaps due to an indirect splanchnic venoconstriction.     

Effects of labetalol on left ventricular mass and function in hypertension--an assessment by serial echocardiography

We determined echocardiographic (M-mode) indices of left ventricular mass and function serially at 1-month intervals in 10 patients with uncomplicated mild or moderate essential hypertension, before and after adequate control of blood pressure with labetalol, a combined alpha- and beta-receptor blocking agent. Seven patients had pretreatment echocardiographic evidence of left ventricular hypertrophy with disproportionate septal thickness in 4. Systolic blood pressure in the untreated state correlated well (r = 0.96) with left ventricular mass but poorly (r = 0.30) with diastolic pressure. Following a satisfactory blood pressure reduction, achieved in all patients, left ventricular mass decreased from 240.5 +/- 71.1 g to 159.5 +/- 40.7 g (P less than 0.01), interventricular septal thickness from 1.33 +/- 0.3 cm to 0.92 +/- 0.25 cm (P less than 0.01) and posterior wall thickness from 1.03 +/- 0.23 cm to 0.93 +/- 0.23 cm (P less than 0.05). While the maximum changes in left ventricular mass were noted by the end of first month (P less than 0.01) with insignificant changes thereafter, the correlation of fall in blood pressure with change in left ventricular mass was significant only after 2 months of treatment (P less than 0.05). Indices of left ventricular function (end-diastolic volume, ejection fraction, fractional diameter shortening, left atrial dimension and posterior aortic wall motion) were normal before treatment and remained unchanged during 3 months of treatment. In this short-term study, labetalol reduced left ventricular hypertrophy (expressed as left ventricular mass and wall thickness) without altering left ventricular function indices in patients with uncomplicated essential hypertension. This has important implications in the treatment of hypertensive patients.     

The acute effects of intravenous xamoterol ('Corwin', I.C.I. 118, 587) on resting and exercise haemodynamics in patients with mild to moderate heart failure

The known properties of xamoterol, a partial beta 1-agonist, provide a basis to pharmacologically modulate cardiac responses to variations in sympathetic tone. Haemodynamic variables were assessed at rest and on exercise before and after intravenous xamoterol (0.2 mg kg-1), in 30 patients with mild to moderate cardiac failure. Xamoterol produced significant improvements in resting cardiac index (2.51 +/- 0.15 to 2.80 +/- 0.14 l min-1 m-2; P less than 0.001), stroke volume (62 +/- 4 to 75 +/- 5 mljbeat-1; P less than 0.001) and stroke work index (42.4 +/- 3.6 to 47.7 +/- 3.9 gm beat-1 m-2; P less than 0.01). This occurred despite a significant reduction in heart rate (78 +/- 3 to 74 +/- 2 beats min-1; P less than 0.05). There were also significant reductions in systemic vascular resistance (1990 +/- 141 to 1669 +/- 112 dynes s-1 cm-5; P less than 0.01) and double product (1146 +/- 46 to 1051 +/- 41 mmHg min-1 x 10(-1); P less than 0.05), with no significant changes in systolic blood pressure, pulmonary wedge pressure or ejection fraction. Xamoterol significantly attenuated the heart rate response to exercise (112 +/- 4 to 97 +/- 3 beats min-1; P less than 0.001), with no impairment in the expected exercise induced increase in cardiac index. This was due to the significant increase in stroke volume from 81 +/- 6 to 95 +/- 7 ml beat-1 (P less than 0.001). There were no significant changes in resting or exercise noradrenaline levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Demonstration of dissimilar acute haemodynamic effects of ethanol and acetaldehyde.

To determine whether the acute cardiac depressant effects of ethanol could be attributed to its metabolite (acetaldehyde), either ethanol or acetaldehyde was intravenously infused into pentobarbital anaesthetised, closed-chest dogs. At a venous blood ethanol level of 199 +/- 43 (SE) mg . dl-1, ejection fraction had decreased from 35 +/- 2 to 30 +/-2%, P less than 0.05, max dP/dt/end-diastolic volume from 14.0 +/- 2.1 to 8.6 +/- 1.1 kPa . s-1 . cm-3 (105 +/- 16 to 65 +/- 8 mmHg . s-1 . cm-3), P less than 0.02, whereas end-diastolic volume (P less than 0.005), myocardial oxygen consumption (P less than 0.05) and coronary blood flow (P less than 0.005) had increased. Higher ethanol levels exaggerated these changes when peak arterial acetaldehyde was 20.2 +/- mumol . litre-1. By contrast, infusion of acetaldehyde to a peak blood level comparable with that produced by ethanol increased cardiac output from 2.4 +/- 0.2 to 2.8 +/- 0.2 litre-1 . min-1 P less than 0.01), coronary sinus oxygen saturation from 46 +/- 4 to 55 +/- 3% (P less than 0.25) and reduced systemic resistance from 8.0 +/- 0.7 to 6.3 +/- 0.5 kPa . litre-1 . min-1 (60 +/- 5 to 47 +/- 4 mmHg . litre-1 . min-1) (P less than 0.001). High dosage of acetaldehyde to a level of 129 +/- 23 mumol . litre-1 produced elevation of cardiac output (P less than 0.001), ejection fraction (P less than 0.01), coronary blood flow (P less than 0.02), whereas systemic resistance (P less than 0.001), heart rate (P less than 0.05) and myocardial oxygen consumption (P less than 0.05) decreased. Discontinuation of acetaldehyde infusion significantly reversed these changes. Max dP/dt/left ventricular end-diastolic volume and left ventricular end-diastolic volume were not significantly altered by acetaldehyde. Thus, ethanol depresses cardiac performance and increases myocardial oxygen consumption. By contrast, acetaldehyde at levels produced by ethanol metabolism improves cardiac performance, consequent to afterload reduction, and reduces myocardial oxygen consumption.     

Hemodynamic characteristics of sodium-sensitive human subjects

Fifty-eight normal subjects and 51 subjects with borderline hypertension underwent microvascular and hemodynamic studies while on an ad libitum diet and during periods of sodium depletion (10 mEq/day) and repletion (200 mEq/day). Hemodynamic measurements included arterial blood pressure, cardiac index, total peripheral resistance, forearm blood flow, vascular resistance, venous compliance, and capillary filtration fraction. Studies of the microcirculation consisted of macrophotography of the bulbar conjunctiva with measurement of anteriolar, venular, and capillary density and diameter. During sodium repletion, cardiac index increased significantly in the normal subjects (2.35 +/- 0.7 vs 2.44 +/- 0.7 L/min/m2; p less than 0.01) and in the borderline hypertensive subjects (2.50 +/- 0.7 vs 2.70 +/- 0.8 L/min/m2; p less than 0.01). However, mean blood pressure rose by more than 5% in only 33 subjects, 13 with normal and 20 with borderline hypertension. When these sodium-sensitive subjects were compared with those whose blood pressure did not rise, the former were found to have significantly higher forearm vascular resistance (32.2 +/- 21 vs 17.9 +/- 12 mm Hg/ml/min/100 g; p less than 0.01), lower forearm blood flow (4.42 +/- 2.7 vs 7.47 +/- 5.0 ml/min/100 g) and lower conjunctival capillary density (3.72 +/- 1.7 vs 5.18 +/- 2.1 [SD] mm/mm2; p less than 0.05). These results indicate that sodium sensitivity in humans is accompanied by elevation of forearm vascular resistance and attenuation of the microcirculation.     

Effect of a high carbohydrate, low sodium and low fat diet in type 2 diabetics with moderate hypertension

The effect of an intended diet, high in cereal fibre, low in fat and sodium was assessed over a 3-month period in 13 type 2 diabetic patients with moderate hypertension (diastolic blood pressure greater than 105 and less than 115 mmHg without antihypertension drug therapy). Eleven patients completed the study and two patients were withdrawn owing to an increase of blood pressure above initial values after 1 month. Using a compliance scoring system by an observer unaware of blood pressure response, patients were divided into those compliant to the dietary regimen (n = 7; group A) and those who were not, and therefore were considered controls (n = 4; group B). Group A demonstrated significant reductions in systolic (190.4 +/- 18 to 166.6 +/- 22.4 mmHg; P less than 0.02) and diastolic blood pressure (113.1 +/- 3.7 to 103.3 +/- 9.1 mmHg; P less than 0.01), weight (78.5 +/- 5.6 to 74.3 +/- 6.8 kg; P less than 0.02), daily urinary sodium excretion (210.3 +/- 79.9 to 120.3 +/- 56.1 mmol; P less than 0.02) and serum LDL levels (P less than 0.02). A reduction in glycosylated haemoglobin of 2.2 per cent was also noted. Three patients achieved a diastolic blood pressure level below 100 mmHg. In contrast, no significant changes occurred in group B. In particular, systolic and diastolic blood pressure (111.0 +/- 2.2 to 110.3 +/- 8.9 mmHg) remained unchanged. We conclude that the modified diet may have a hypotensive effect in diabetic subjects with moderate hypertension. However, the degree of blood pressure reduction suggests that this diet could, at best, only be considered an adjunct to conventional antihypertensive drug therapy.     

Effect of adrenal suppression with dexamethasone in essential hypertension.

The 24-h integrated plasma concentration of aldosterone (IC-ALDO), PRA (IC-PRA), and cortisol (IC-F) were measured in 34 male patients with uncomplicated mild essential hypertension and 15 matched normal controls using a portable 24-h continuous nonthrombogenic blood withdrawal system. The hypertensive were subsequently given 0.5 mg dexamethasone three times per day, resulting in suppression of their urinary excretion of 17-hydroxycorticosteroids and free cortisol. The diastolic blood pressure of the hypertensives fell during adrenal suppression from 104 +/- 5 to 96 +/- 8 mm Hg (mean +/- 1 SD; P less than 0.0001). The systolic pressure fell from 150 +/- 16 to 148 +/- 17 (P greater than 0.01). Baseline values for IC-F, IC-ALDO, and IC-PRA were similar in hypertensive subjects and normal controls. After treatment with dexamethasone for 8 weeks, IC-F in the hypertensives decreased from 7.8 +/- 2.1 to 0.7 +/- 0.6 microgram/dl (P less than 0.0001). There was no associated change in IC-ALDO or IC-PRA. Thus, the fall in diastolic blood pressure in response to dexamethasone was associated with suppression of IC-F, without demonstrable changes in other endocrine or biochemical factors measured.     

Studies on abnormalities of adrenal steroidogenesis in essential hypertension, primary aldosteronism and renovascular hypertension: responses of plasma steroids to angiotensin III

In the present study, effects of angiotensin on the adrenal steroidogenesis were studied in essential hypertension, primary aldosteronism and renovascular hypertension (RVH). Angiotensin III(A III), an analogue of angiotensin II, was administered to 17 normal volunteers (9 male and 8 female), 44 patients with essential hypertension (EH) (15 with high renin; HREH, 15 with normal renin; NREH and 14 with low renin; LREH), 8 patients with primary aldosteronism (5 with adrenal adenoma; APA and 3 with bilateral adrenocortical hyperplasia; IHA) and 5 patients with renovascular hypertension. In all the patients with hypertension and normal subjects, blood pressure (BP) and plasma concentrations of progesterone (P), corticosterone (B), aldosterone (Aldo), 17 alpha-hydroxyprogesterone(17-OHP) and cortisol(F) were measured before and after intravenous administration of A III (0.1, 0.5, 1.0, 10, 20 and 40 ng/kg/min, for 15 min, respectively). 1) BP rose from 164 +/- 19/88 +/- 8 to 180 +/- 19/112 +/- 10 mmHg [systolic BP(SBP); P less than 0.01, diastolic BP(DBP); P less than 0.01] in HREH, from 162 +/- 12/96 +/- 7 to 186 +/- 11/118 +/- 8 mmHg in NREH(SBP; P less than 0.01, DBP; P less than 0.01), 165 +/- 12/94 +/- 8 to 202 +/- 12/126 +/- 9 mmHg in LREH(SBP; P less than 0.001, P less than 0.001) and 118 +/- 8/72 +/- 7 mmHg to 136 +/- 11/88 +/- 8 mmHg in controls (SBP; P less than 0.01, DBP; P less than 0.01). The elevation in NREH and LREH was greater than that in HREH and controls. The elevations of BP both in APA and IHA were remarkably greater than that in controls and as similar as LREH(APA; 174 +/- 21/103 +/- 12 to 204 +/- 18/136 +/- 8 mmHg, IHA; 176 +/- 10/104 +/- 4 to 206 +/- 17/138 +/- 10 mmHg). The elevation in RVH was similar to that in NREH(173 +/- 9/108 +/- 8 to 194 +/- 13/132 +/- 10 mmHg). 2) Plasma P increased from 25.5 +/- 7.5 to 39.5 +/- 13.8 ng/100 ml(P less than 0.001) in HREH, from 28.0 +/- 7.7 to 45.3 +/- 12.7 ng/100 ml(P less than 0.001) in NREH, from 23.8 +/- 8.2 to 47.2 +/- 19.4 ng/100 ml(P less than 0.001) in LREH and 26.6 +/- 11.0 to 43.4 +/- 14.6 ng/100 ml in controls. The increment in HREH or NREH was similar to that in controls(P less than 0.1, respectively), whereas greater than controls in LREH(P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)     

Nicardipine Infusion Improved Hepatic Function But Failed to Reduce Hepatic Venous Pressure Gradient in Patients with Cirrhosis

We investigated the effects of nicardipine on systemic and splanchnic hemodynamics and on liver function in 16 patients with cirrhosis and portal hypertension. Patients received a continuous infusion of 0.3 mg/min of nicardipine (n = 10) and a control infusion (n = 6). No significant changes were observed after a control infusion. In contrast, systemic vasodilatation, evidenced by a significant fall in mean arterial pressure (-14%, p less than 0.01) and systemic vascular resistance (-30%, p less than 0.01), increased heart rate (+8%, p less than 0.01) and cardiac output (+21%, p less than 0.01), and increased hepatic blood flow (+43%, p less than 0.01) were observed at 60 min after a continuous infusion of nicardipine. Although nicardipine improved hepatic function (intrinsic clearance from 0.29 +/- 0.13 to 0.33 +/- 0.15 L/min, p less than 0.05), portal pressure evaluated by hepatic venous pressure gradient was not reduced significantly (from 16.3 +/- 4.9 to 15.1 +/- 5.7 mm Hg; NS). We conclude that a continuous infusion of nicardipine improves liver function but has no beneficial effect on portal pressure in patients with cirrhosis.     

Relationship between plasma atrial natriuretic peptide and left atrial and left ventricular involvement in essential hypertension

In order to investigate the role of cardiac hypertrophy in atrial natriuretic peptide (ANP) secretion in patients with essential hypertension, plasma levels of ANP were measured after overnight rest in 36 patients with untreated hypertension and in 31 normotensive controls. In the hypertensive subjects, plasma levels were correlated with left ventricular (LV) and left atrial abnormalities detected by chest X-ray, electrocardiogram (ECG) and M-mode echocardiography. Plasma ANP levels in patients with hypertension averaged 146 +/- 27 pg/ml compared to 46 +/- 7 pg/ml in the normotensive subjects (P less than 0.001). In patients with hypertension a significant correlation was found between ANP and supine systolic blood pressure (r = 0.54, P less than 0.001) and between ANP and diastolic blood pressure (r = 0.38, P less than 0.05). Furthermore, plasma ANP levels were correlated with total heart volume (r = 0.68, P less than 0.01), LV mass (r = 0.525, P less than 0.001), LV posterior wall thickness (r = 0.39, P less than 0.05), Sokolow-Lyon index (r = 0.721, P less than 0.001) and end-diastolic diameter of the left atrium (r = 0.334, P less than 0.05). The results suggest a contribution of LV and left atrial abnormalities to ANP secretion in essential hypertension.     

Effect of acebutolol on left ventricular hemodynamics and anatomy in systemic hypertension

In 18 patients with mild or moderate essential hypertension who responded favorably to acebutolol antihypertensive therapy, echocardiography (echo) was performed in the basal condition and after 6 and 12 months of follow-up. Acebutolol induced a significant decrease in blood pressure (BP), from a basal value of 167 +/- 3/105 +/- 2 mm Hg to 138 +/- 5/90 +/- 2 mm Hg after 6 months (p less than 0.01) and to 134 +/- 3/91 +/- 3 mm Hg after 1 year (p less than 0.01), and in heart rate, from 75 +/- 3 to 63 +/- 2 beats/min after 6 months (p less than 0.01) and to 63 +/- 2 beats/min after 1 year (p less than 0.01). The decrease in BP was achieved through a decrease in cardiac output from 6.3 +/- 0.28 to 5.3 +/- 0.25 liters/min after 6 months (p less than 0.05) and to 5.32 +/- 0.2 liters/min after 1 year (p less than 0.05), which resulted from a reduction in heart rate; stroke volume did not show significant change during the treatment and left ventricular (LV) performance was improved. There was a parallel decrease in LV posterior wall and ventricular septal thicknesses and estimated LV mass. In patients with LV hypertrophy, the change in mass was significantly correlated with the change in heart rate both after 6 and 12 months of therapy (r = 0.6234, p less than 0.05 and r = 0.7121, p less than 0.05 after 6 and 12 months, respectively).     

Oxygen delivery and utilization during rapidly fatal septic shock in rats

Oxygen delivery and utilization were studied in a rapidly fatal model of rat peritonitis. Cecal ligation and perforation induced peritonitis and septic shock in five animals. Five animals served as sham-operated controls. Arterial pressure, central venous pressure, cardiac index, hemoglobin, plasma colloid osmotic pressure, arterial blood lactate concentration, and arterial and central venous oxygen saturation were sequentially measured over 5 hr. In septic animals, decreases in mean central venous pressure were associated with hemoconcentration and decreases in plasma colloid osmotic pressure from 16.3 +/- 0.8 to 12.2 +/- 0.1 mmHg (P less than 0.05). The cardiac index decreased from 359 +/- 35 to 166 +/- 25 ml/kg/min (P less than 0.001), and arterial lactate increased from 0.2 +/- 0.1 to 2.1 +/- 0.4 mmol (P less than 0.001). However, oxygen consumption was maintained secondary to increases in systemic oxygen extraction. Arterial lactate concentration was inversely correlated with systemic oxygen delivery and central venous oxygen saturation (r = -0.68, P less than 0.05 and r = -0.71, P less than 0.001, respectively). These observations during lethal peritonitis suggest that hypovolemia is associated with increases in microvascular permeability, although the concomitant influence of intravascular pooling cannot be excluded. Decreases in systemic perfusion appear to account for critical oxygen deficits and lactic acidosis. The increases in systemic oxygen extraction imply that cellular oxygen utilization is maintained during lethal septic shock.