Hydrocortisone-induced hypertension in humans: pressor responsiveness and sympathetic function

Oral hydrocortisone increases blood pressure and enhances pressor responsiveness in normal human subjects. We studied the effects of 1 week of oral hydrocortisone (200 mg/day) on blood pressure, cardiac output, total peripheral resistance, forearm vascular resistance, and norepinephrine spillover to plasma in eight healthy male volunteers. Although diastolic blood pressure remained unchanged, systolic blood pressure increased from 119 to 135 mm Hg (SED +/- 3.4, p less than 0.01), associated with an increased cardiac output (5.85-7.73 l/min, SED +/- 0.46, p less than 0.01). Total peripheral vascular resistance fell from 15.1 to 12.2 mm Hg/l/min (SED +/- 1.03, p less than 0.05). Resting forearm vascular resistance remained unchanged, but the reflex response to the cold pressor test was accentuated, the rise in resistance increasing from 10.5 mm Hg/ml/100 ml/min (R units) before treatment to 32.6 R units after treatment (SED +/- 6.4, p less than 0.025). The rise in forearm vascular resistance accompanying intra-arterial norepinephrine (25, 50, and 100 ng/min) was also significantly greater after hydrocortisone, increasing from an average of 14.9 +/- 2.4 R units before treatment to 35.1 +/- 5.5 R units after hydrocortisone (SED +/- 6.0, p less than 0.05). A shift to the left in the dose-response relation and fall in threshold suggested increased sensitivity to norepinephrine after treatment. Measurement of resting norepinephrine spillover rate to plasma and norepinephrine uptake indicated that overall resting sympathetic nervous system activity was not increased. The rise in resting blood pressure with hydrocortisone is associated with an increased cardiac output (presumably due to increased blood volume).(ABSTRACT TRUNCATED AT 250 WORDS)     

Peripheral circulatory effects of insulin in diabetes

Peripheral circulatory effects of insulin were studied in the diabetic patients with and without autonomic neuropathy. Forearm blood flow, calf venous volume and calf venous distensibility were measured by strain gauge plethysmography. In the diabetic patients with autonomic neuropathy, mean blood pressure fell from 96 +/- 5 to 88 +/- 5 mmHg after an intravenous injection of 4 U of monocomponent insulin (p less than 0.001). Forearm vascular resistance decreased from 53.99 +/- 8.29 to 45.88 +/- 7.76 mmHg X ml-1 X 100ml-1 X min-1 after insulin (p less than 0.01). Insulin increased calf venous volume from 1.20 +/- 0.19 to 2.23 +/- 0.44 ml/100ml (p less than 0.05) and calf venous distensibility from 0.039 +/- 0.004 to 0.082 +/- 0.016 ml/mmHg (p less than 0.05). In contrast, in the diabetic patients without autonomic neuropathy, there were no significant changes in the mean blood pressure, forearm vascular resistance, calf venous volume and calf venous distensibility. Symptoms of hypoglycaemia did not occur in any patient. These results suggest that insulin has a vasodilator action on both resistance and capacitance vessels, which may be one of the main factors in insulin-induced hypotension.     

Sympathetic vasoconstriction during exercise in ambulatory patients with left ventricular failure

In patients with heart failure, exercise is thought to increase sympathetic vasoconstrictor tone. To investigate the extent of this sympathetic activation, we studied the effect of maximal exercise on nonexercising vascular beds in 35 patients with left ventricular failure (ejection fraction, 21 +/- 8%; peak exercise oxygen uptake (VO2), 12.3 +/- 3.5 ml/min/kg). In 28 patients, cardiac output and leg blood flow were measured during maximal upright bicycle exercise. Total flow to nonexercising tissue was then calculated as cardiac output--(2 x leg flow). In seven patients and six normal subjects, forearm blood flow was measured during supine bicycle exercise before and after alpha-adrenergic blockade with intravenous phentolamine. Maximal upright exercise increased the vascular resistance of nonexercising tissue from 34 +/- 16 units at upright rest to 45 +/- 25 units (p less than 0.02) but did not affect total flow to nonexercising tissue (rest, 2.9 +/- 1.0; maximal exercise, 2.8 +/- 1.4 l/min; p = NS). Supine exercise had no significant effect on forearm blood flow or vascular resistance in the normal subjects. In the patients with heart failure, supine exercise increased forearm vascular resistance from 45 +/- 17 to 58 +/- 25 mm Hg/ml/min/100 ml (p less than 0.02), again with no change in tissue flow (rest, 2.4 +/- 0.1; maximal exercise, 2.4 +/- 0.9 ml/min/100 ml; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Vasodilatory behavior of skeletal muscle arterioles in patients with nonedematous chronic heart failure

During maximal upright exercise, blood flow to working skeletal muscle is frequently reduced in patients with nonedematous chronic heart failure. It has been speculated that this reduced muscle flow may be caused in part by an intrinsic impairment of skeletal muscle vasodilatory capacity. To test this hypothesis, forearm blood flow and resistance were compared during forearm exercise and in response to transient forearm ischemia (10 min) in 22 patients with heart failure and in 11 normal subjects. During forearm exercise, both groups exhibited comparable forearm blood flows (ml/min/100 ml) (0.2 W: normal 5.9 +/- 3.1, heart failure 6.5 +/- 2.8; 0.4 W: normal 8.2 +/- 5.5, heart failure 8.2 +/- 3.6; 0.6 W: normal 11.5 +/- 6.8, heart failure 11.8 +/- 4.8 [all p = NS]) and forearm vascular resistance (mm Hg/ml/min/100 ml) (0.2 W: normal 23.1 +/- 12.4, heart failure 18.5 +/- 7.8; 0.4 W: normal 16.9 +/- 7.7, heart failure 14.7 +/- 6.4; 0.6 W: normal 13.1 +/- 7.7, heart failure 10.3 +/- 4.1 [all p = NS]). Ten minutes of forearm ischemia, an intervention that produces maximal forearm vasodilation, also resulted in comparable forearm vascular resistances in both groups (normal 4.1 +/- 2.4, heart failure 3.8 +/- 1.3 mm Hg/ml/min/100 ml/p = NS). These data suggest that skeletal muscle vasodilatory capacity is not intrinsically impaired in patients with nonedematous chronic heart failure.     

Coronary and systemic hemodynamic effects of nicardipine

Systemic and coronary hemodynamic effects of a new dihydropyridine calcium antagonist, nicardipine, were studied in 15 patients. Nicardipine was administered as a 2-mg bolus intravenously followed by an infusion titrated to maintain a 10 to 20-mm Hg decrease in systolic pressure. Nicardipine increased both heart rate from 69 +/- 3 to 81 +/- 3 beats/min and cardiac output from 7.3 +/- 0.5 to 9.9 +/- 0.5 liters/min (both p less than 0.001) as systemic vascular resistance decreased from 1,183 +/- 70 to 733 +/- 33 dynes s cm-5 (p less than 0.001). Left ventricular end-diastolic pressure remained constant, at 14 +/- 1 vs 14 +/- 1 mm Hg as stroke volume increased from 108 +/- 6 to 123 +/- 6 ml/m2 (p less than 0.001). Coronary blood flow increased from 102 +/- 9 to 147 +/- 13 ml/min, while coronary resistance decreased from 1.17 +/- 0.1 to 0.7 +/- 0.1 mm Hg/ml/min (both p less than 0.001). Heart rate-systolic blood pressure product did not change (104 +/- 5 vs 106 +/- 5 beats/min mm Hg X 10(-2), difference not significant) with drug administration. At the same heart rate before and during nicardipine administration (using atrial pacing in 6 patients), significant augmentation of coronary flow was still observed. Thirteen of 14 patients showed a greater percent decrease in coronary resistance than systemic vascular resistance. Nicardipine differs from other calcium antagonists with respect to consistent augmentation of coronary blood flow. This effect appears to be the result, in part, of increased potency in the coronary bed compared with the systemic vascular bed.     

New insights into pacemaker syndrome gained from hemodynamic, humoral and vascular responses during ventriculo-atrial pacing

Ventricular pacing is performed during programmed electrical stimulation and during normal functioning of single chamber (VVI or VVIR) pacemakers. In many patients, retrograde ventriculoatrial (V-A) conduction may occur and evoke hemodynamic and reflex neurohumoral responses, which are unique to this pacing mode. Accordingly, forearm blood flow, forearm vascular resistance, mean and phasic arterial pressure, cardiac output and plasma norepinephrine, epinephrine and dopamine were measured during atrial, ventricular and V-A pacing at a cycle length of 600 ms (100 beats/min) before and after regional alpha blockade with intraarterial phentolamine in 16 patients with a left ventricular ejection fraction greater than 35% and little or no symptoms of congestive heart failure. During V-A pacing, cardiac output decreased by 10%, whereas forearm vascular resistance increased from 52 +/- 7 to 70 +/- 9 U (p less than 0.001) and plasma norepinephrine increased from 183 +/- 27 to 232 +/- 27 pg/ml (p less than 0.01). Phentolamine nearly abolished the increase in forearm vascular resistance in response to V-A pacing (18 +/- 4.1 U before vs 5.8 +/- 1.5 U after, p less than 0.05). The change in forearm vascular resistance with V-A pacing correlated with systolic arterial pressure, but not with changes in mean arterial pressure, pulse pressure, cardiac output, mean or peak right atrial pressure, pulmonary artery or pulmonary capillary wedge pressure. These results suggest that forearm vascular resistance responses to V-A pacing are mediated mainly by alpha-adrenergic receptors, through the arterial baroreflexes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Splanchnic Hemodynamics in Idiopathic Portal Hypertension: Comparison with Chronic Persistent Hepatitis

A comparative study of splanchnic hemodynamics was made in 12 patients with idiopathic portal hypertension and in eight patients with chronic persistent hepatitis, but without portal hypertension, who served as the control. Venous pressures were measured by portal and hepatic vein catheterizations, blood flow by the pulsed Doppler flowmeter, and organ volume by computed tomography. Splenic artery blood flow was 788 +/- 242 ml/min in idiopathic portal hypertension and about four times that in chronic persistent hepatitis (215 +/- 42 ml/min), whereas there was no difference in superior mesenteric artery blood flow between the former and the latter (408 +/- 142 vs. 389 +/- 32 ml/min). Spleen volume in idiopathic portal hypertension was six times that in chronic persistent hepatitis, and splenic artery blood flow showed a significant linear correlation with spleen volume in idiopathic portal hypertension (r = 0.71, p less than 0.02). The sum of splenic artery blood flow and superior mesenteric artery blood flow in idiopathic portal hypertension was 1195 +/- 294 ml/min, twice that in chronic persistent hepatitis (603 +/- 109 ml/min). Portal vascular resistance and intrahepatic portal vascular resistance were three times and four times those in chronic persistent hepatitis, respectively. These results indicate that both increased intrahepatic portal vascular resistance and increased splenic artery blood flow may play roles in the development of portal hypertension in idiopathic portal hypertension.     

Systemic and coronary effects of intravenous milrinone and dobutamine in congestive heart failure

The effects of dobutamine and intravenous milrinone on systemic hemodynamics, coronary blood flow and myocardial metabolism were studied in 11 patients with severe congestive heart failure. Although milrinone and dobutamine similarly increased cardiac index from 1.9 +/- 0.4 to 2.5 +/- 0.4 liters/min per m2 (p less than 0.001) and from 1.9 +/- 0.4 to 2.8 +/- 0.8 liters/min per m2 (p less than 0.001), respectively, milrinone decreased left ventricular end-diastolic pressure to a greater extent than dobutamine, that is, from 26 +/- 6 to 12 +/- 8 mm Hg (p less than 0.001) versus 26 +/- 8 to 20 +/- 8 mm Hg (p less than 0.001). In contrast to dobutamine, milrinone significantly reduced mean systemic arterial and right atrial pressures. Dobutamine increased the first derivative of left ventricular pressure (dP/dt) from 1,013 +/- 309 to 1,360 +/- 538 mm Hg/s (p less than 0.01) but milrinone did not. Similarly, blood flow and myocardial oxygen consumption were increased by dobutamine from 152 +/- 87 to 187 +/- 118 ml/min (p less than 0.05) and from 17.7 +/- 10.9 to 21.5 +/- 14.9 ml O2/min (p less than 0.05), respectively, but were unchanged by milrinone. Both drugs significantly decreased coronary vascular resistance and myocardial oxygen extraction but did not change myocardial lactate extraction. Thus, dobutamine and milrinone produce similar improvement in cardiac index. However, dobutamine increases myocardial oxygen consumption, whereas milrinone does not. This difference can probably be explained by the substantial vasodilating properties of milrinone.     

Resting and maximal forearm skin blood flows are reduced in hypertension.

To find whether the vasodilator capacity of nonacral skin is reduced in hypertension, we measured forearm blood flow by venous occlusion plethysmography in 10 seated normotensive (mean +/- SD mean arterial pressure, 94 +/- 5 mm Hg) and 10 hypertensive (112 +/- 9 mm Hg) men at rest for 39 minutes while the forearm was heated with water at 42 degrees C, a maneuver known to selectively and maximally vasodilate skin. Blood pressure, measured every 5 minutes, did not change with heating. We found that in the normotensive group resting forearm blood flow was higher (3.64 +/- 1.12 versus 2.48 +/- 0.58 ml/100 ml tissue per minute, p less than 0.001; normotensive group versus hypertensive group) and resting forearm vascular resistance lower (30.17 +/- 10.99 versus 48.88 +/- 17.37 mm Hg.min.100 ml tissue per minute, p less than 0.05; normotensive group versus hypertensive group), and maximal forearm blood flow with local heating was higher (29.32 +/- 11.99 versus 18.19 +/- 4.50 ml/100 tissue per minute, p less than 0.018; normotensive group versus hypertensive group and vascular resistance lower (4.07 +/- 1.04 versus 6.54 +/- 1.17 mm Hg.min.100 ml tissue per minute, p less than 0.005; normotensive group versus hypertensive group). To find whether this degree and duration of local warming maximally vasodilated the skin in hypertensive subjects (as it does in normotensive subjects), we measured forearm skin blood flow before and during local heating plus 10 minutes of ischemia using a laser Doppler flowmeter.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immediate and short-term hemodynamic effects of diltiazem in patients with hypertension

The immediate effects of intravenous diltiazem effects and short-term (4 weeks) of the oral drug on systemic and regional hemodynamics, cardiac structure, and humoral responses were evaluated by previously reported methods in nine patients with mild-to-moderate essential hypertension and in one patient with primary aldosteronism. Diltiazem was first administered in three intravenous doses of 0.06, 0.06, and 0.12 mg/kg, respectively; patients were then treated for 4 weeks with daily doses ranging from 240 to 360 mg (average 300 mg). Intravenous diltiazem immediately reduced mean arterial pressure (from 115 +/- 3 to 96 +/- 3 mm Hg; p less than .01) through a fall in total peripheral resistance index (from 37 +/- 3 to 23 +/- 2 U/m2; p less than .01) that was associated with an increase in heart rate (from 66 +/- 2 to 77 +/- 3 beats/min; p less than .01) and cardiac index (from 3.3 +/- 0.3 to 4.3 +/- 0.4 liters/min/m2; p less than .01). These changes were not associated with changes in plasma levels of catecholamines or aldosterone or in plasma renin activity. After 4 weeks the significant decrease in mean arterial pressure persisted (104 +/- 3 mm Hg; p less than .01) and there were still no changes in the humoral substances or plasma volume. Renal blood flow index increased (from 368 +/- 52 to 462 +/- 57 ml/min/m2; p less than .01) and renal vascular resistance index decreased (from 0.37 +/- 0.06 to 0.26 +/- 0.04 U/m2; p less than .01), while splanchnic hemodynamics did not change.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of prostaglandin inhibition on systemic and hepatic hemodynamics in patients with cirrhosis of the liver

The role of prostaglandins in the pathogenesis of the circulatory abnormalities of cirrhosis was investigated by studying the effects of prostaglandin inhibition with indomethacin (50 mg/8 h for 24 h) on the systemic and splanchnic hemodynamics in 13 patients with cirrhosis of the liver. Indomethacin administration significantly reduced cardiac output (from 7.44 +/- 0.7 to 6.78 +/- 0.7 L/min, p less than 0.05) and increased peripheral vascular resistance (from 990 +/- 104 to 1155 +/- 140 dyn X s X cm-5, p less than 0.05). Arterial pressure was not modified. These changes in systemic hemodynamics were associated with a significant reduction in hepatic blood flow (from 1.88 +/- 0.43 to 1.48 +/- 0.3 L/min, p less than 0.05) and with a slight decrease of portal pressure (from 18.8 +/- 1.3 to 17.5 +/- 1.4 mmHg, p less than 0.05). These results suggest that endogenous prostaglandins contribute to the increased cardiac output and diminished vascular resistance observed in cirrhosis of the liver. In addition, by promoting splanchnic vasodilation, prostaglandins may contribute to increased portal pressure in these patients.     

Hyperdynamic circulation in a chronic murine schistosomiasis model of portal hypertension

Chronic murine schistosomiasis is a natural disease model of portal hypertension closely mimicking the clinical and histological features of human hepatic schistosomiasis. We studied the splanchnic and systemic hemodynamics in the murine model of schistosomiasis by radioactive microsphere technique. Mice infected with 60 cercariae of Schistosoma mansoni (n = 8) were studied hemodynamically 11 wk after the infection and were compared with age-matched healthy controls (n = 11). Mean portal venous inflow in the infected mice (3.82 +/- 0.32 ml/min) was 61% higher than in the healthy animals (2.37 +/- 0.25 ml/min; p less than 0.01). A twofold increase in hepatic arterial flow was also seen in mice with schistosomiasis (0.47 +/- 0.14 ml/min) as compared with controls (0.16 +/- 0.03 ml/min; p less than 0.05), whereas splanchnic arteriolar resistance (60.91 +/- 7.64 vs. 101.21 +/- 11.06 mm Hg.min.ml-1.gm; p less than 0.05) and peripheral vascular resistance (112.05 +/- 14.05 vs 254.53 +/- 29.86 mm Hg.min.ml-1.gm; p less than 0.01) were reduced. There was a significant increase in cardiac index (752 +/- 99 vs. 453 +/- 55 ml.min-1.kg body weight-1; p less than 0.05) and reduction in mean arterial pressure (81.37 +/- 3.09 vs. 101.45 +/- 5.85 mm Hg; p less than 0.05) in the infected animals compared with controls. These observations clearly demonstrate the existence of a hyperdynamic circulatory state in this model of portal hypertension.     

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.     

MDL 17,043: short- and long-term cardiopulmonary and clinical effects in patients with heart failure

MDL 17,043, an inotropic and vasodilator drug, is believed to have beneficial effects in patients with heart failure. Its short- and long-term hemodynamic and cardiopulmonary effects were studied in 10 patients with New York Heart Association functional class III heart failure who were maintained on digitalis and diuretic drugs. Hemodynamics at baseline study and after 24 hours of oral therapy (four doses of 6 mg/kg) showed increased cardiac output (3.9 +/- 0.7 to 6.1 +/- 1.1 liters/min, p less than 0.05), increased stroke volume (42 +/- 12 to 60 +/- 15 ml, p less than 0.05), decreased systemic vascular resistance (1,564 +/- 326 to 1,009 +/- 296 dynes X s X cm-5, p less than 0.05) but no change in pulmonary capillary wedge pressure (31 +/- 6 to 25 +/- 13 mm Hg, p = NS). Only systemic vascular resistance and arteriovenous oxygen difference were significantly decreased during exercise. When restudied after 5 weeks of therapy, neither cardiac output nor stroke volume showed a sustained increase at rest or during exercise, and effects on systemic vascular resistance and arteriovenous oxygen difference were not sustained at exercise (p = NS). Peak oxygen uptake during exercise was 8.1 +/- 2.5 ml/kg per min at baseline and was not significantly increased either acutely (9.2 +/- 2.4 ml/kg per min, p = NS) or chronically (8.9 +/- 2.2 ml/kg per min, p = NS). Problems of increased ventricular arrhythmias and diarrhea were noted after therapy was begun.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal hemodynamic effects of vasodilation with nifedipine and hydralazine in patients with heart failure

The central and renal hemodynamic effects of nifedipine were evaluated in nine patients with severe chronic congestive heart failure. Oral nifedipine (34 +/- 22 mg, mean +/- standard deviation) was associated with a decrease in systemic vascular resistance from 1,748 +/- 436 to 1,321 +/- 302 dynes . s . cm-5 (p less than 0.001) and mean arterial blood pressure from 96 +/- 11 to 87 +/- 6 mm Hg (p less than 0.05) and with an increase in cardiac output from 4.2 +/- 1.1 to 4.9 +/- 1.2 liters/min (p less than 0.001). Although renal vascular resistance decreased from 11,988 +/- 2,256 to 10,286 +/- 3,011 dynes . s . cm-5 (p less than 0.05), no significant change was seen in renal blood flow (599 +/- 120 to 640 +/- 162 ml/min), glomerular filtration rate (62 +/- 18 to 62 +/- 17 ml/min), filtration fraction (18 +/- 5 to 17 +/- 6%), the ratio of renal/systemic vascular resistance (7.0 +/- 1.0 to 7.9 +/- 1.8) and the ratio of renal blood flow/cardiac output (0.15 +/- 0.02 to 0.13 +/- 0.03). Intravenous hydralazine (10 +/- 5 mg), given to eight of the patients in a randomized crossover design, resulted in a larger increase in cardiac output than did nifedipine (38 +/- 7 versus 19 +/- 10%, p less than 0.001) and in an increase in total renal blood flow from 570 +/- 152 to 645 +/- 174 ml/min (p less than 0.001). Renal vascular resistance decreased from 12,080 +/- 2,934 to 10,153 +/- 2,372 dynes . s . cm-5 (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional blood flow response to orthostasis in patients with congestive heart failure

To investigate the central and regional circulatory response to orthostasis in congestive heart failure, hemodynamic variables and forearm and hepatic blood flow were measured in 22 patients at supine rest and during a 65 degrees head-up tilt. Results were compared with those in nine normal subjects. Heart rate and mean arterial blood pressure increased during tilt in normal subjects, but not in patients with heart failure. Forearm blood flow decreased in normal subjects from 3.7 +/- 1.1 to 2.7 +/- 1.5 ml/min per 100 g (probability [p] less than 0.02), but did not change from a lower baseline (1.65 +/- 0.78 ml/min per 100 g) in patients. Forearm vascular resistance increased in normal subjects but not in patients. Hepatic blood flow did not change during tilt in either group, but hepatic vascular resistance increased in normal subjects from 0.37 +/- 0.13 to 0.47 +/- 0.15 U, (p less than 0.02). The increase was not seen in patients (1.2 +/- 1.1 to 1.4 +/- 1.0 U, p = not significant [NS] ). Total systemic resistance increased in patients from 1,848 +/- 560 to 2,132 +/- 731 dynes.s.cm-5 (p less than 0.005) indicating that resistance did increase in some vascular beds. Plasma norepinephrine also increased modestly in these patients from 665 +/- 377 to 761 +/- 379 pg/ml (p = 0.035), but individual changes in plasma norepinephrine did not correlate with changes in hepatic or forearm resistance. Thus, both the overall hemodynamic response and the regulation of regional blood flow and resistance differ in several respects in patients with congestive heart failure when compared with normal subjects. Changes in heart rate, blood pressure, forearm flow and forearm and hepatic vascular resistance are all blunted in patients. Reasons for the differences are not yet clear, but may be associated with abnormalities in reflex control of the circulation in patients with congestive heart failure.     

Effects of indomethacin on systemic and coronary hemodynamics in patients with coronary artery disease

The effects and possible mechanisms of actions of indomethacin on systemic and coronary hemodynamics were studied in 17 patients with coronary artery disease. Group I patients (12) were given either indomethacin or placebo in the absence of prior cyclooxygenase inhibition and group II (five) were given indomethacin after prior treatment with 2600 mg of aspirin. In group I, systolic blood pressure rose from a baseline of 136 +/- 5 mm Hg to a peak level of 158 +/- 8 mm Hg 5 minutes after drug (p less than 0.01). This was associated with a fall in coronary blood flow and a rise in coronary vascular resistance from a baseline of 1.36 +/- 0.4 mm Hg/ml/min to 1.99 +/- 0.7 mm Hg/ml/min 5 minutes after indomethacin (p less than 0.01). Immunoreactive thromboxane B2 levels fell from 191 to 1.4 ng/ml. No changes were noted in plasma renin activity, angiotensin II, or catecholamine levels. Immunoreactive thromboxane B2 levels were undetectable throughout the study period in group II patients and the blood pressure response to indomethacin was attenuated. Baseline coronary blood flow was significantly higher (p less than 0.01) and baseline coronary vascular resistance significantly lower (p less than 0.01) than in group I. At all time points after indomethacin, the fall in coronary blood flow was greater and the increase in coronary vascular resistance less in group II versus group I (p less than 0.001). These findings suggest a dissociation between the effect of indomethacin on systemic and coronary hemodynamics, the former apparently being more prostaglandin-dependent than the latter.     

Effects of diltiazem and long-term beta 1-adrenergic blockade on hemodynamics and blood flow during exercise in patients with stable angina pectoris

The short-term effects of oral diltiazem on hemodynamics and distribution of cardiac output at rest and during semiupright bicycle exercise were evaluated in eight patients with stable effort angina on long-term beta 1-adrenergic blockade. Cardiac output and iliofemoral blood flow were measured using thermodilution. The patients were exercised to the same work load on a bicycle before and 2 h after oral diltiazem (60 mg in two patients and 120 mg in six). At maximal exercise, diltiazem reduced heart rate from 94 +/- 5 to 88 +/- 6 beats/min (p less than 0.01), mean arterial pressure from 139 +/- 5 to 127 +/- 4 mm Hg (p less than 0.01) and systemic vascular resistance from 9.7 +/- 0.7 to 8.4 +/- 0.4 x 10(2) dynes.s.cm-5 (p less than 0.05) compared with control. During exercise, cardiac output, iliofemoral blood flow, mean pulmonary wedge pressure and mean right atrial pressure were not altered, but stroke volume increased from 119 +/- 11 to 131 +/- 10 ml (p less than 0.05). Maximal ST segment depression during exercise was decreased and angina was less. Diltiazem does not alter the distribution of the cardiac output during exercise but improves ischemia.     

Skeletal muscle blood flow and venous capacitance in patients with severe sepsis and systemic hypoperfusion

Alterations in peripheral vascular tone are presumed to contribute to circulatory failure during severe sepsis. Decreased venous tone with venous pooling may decrease effective circulatory blood volume, while decreased arterial tone with redistribution of systemic blood may compromise tissue nutrient flow. We compared forearm arterial and venous tone and forearm blood flow in ten patients with and ten patients without sepsis. The FVT, MVC, and FBF were measured by air plethysmography. In the septic patients, MCV was 1.4 +/- 0.1 ml compared with 3.1 +/- 0.2 ml in nonseptic patients (p less than 0.01). The FVT was 13.4 +/- 1.0 mm Hg/ml in septic patients versus 7.0 +/- 0.5 mm Hg/ml in nonseptic patients (p less than 0.01). The ratio of FBF to cardiac output was 0.28 +/- 0.07 percent in septic patients and 0.31 +/- 0.07 percent in nonseptic patients. These data suggest that increased peripheral venous capacitance and redistribution of skeletal muscle blood flow are not present in patients with sepsis.     

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.