Effects of amlodipine and isosorbide dinitrate on exercise-induced and ambulatory ischemia in patients with chronic stable angina pectoris

This study was designed to compare once-daily administration of 5-10 mg amlodipine with two daily doses of 40 mg sustained-release isosorbide dinitrate in 59 patients with stable angina using a randomized, double-blind, crossover study design. Anginal episodes, nitroglycerin consumption, and possible adverse events were recorded in a diary. A maximal symptom-limited bicycle exercise test and 48-hour ambulatory ECG monitoring were performed at baseline and at the end of each 5-week period of therapy. Exercise time, time to angina, time to ST depression, and maximal ST depression were measured during exercise. During ambulatory monitoring, the number of ischemic episodes and the duration per hour of ST depression were assessed. Amlodipine significantly reduced anginal episodes (P < 0.001) when compared with isosorbide dinitrate. Furthermore, amlodipine prolonged time to ST depression (P < 0.001) and time to angina (P < 0.05) when compared with isosorbide dinitrate. The number and duration of ischemic episodes during ambulatory monitoring were significantly reduced with amlodipine when compared with baseline values (P < 0.05), whereas no differences were found between isosorbide dinitrate and baseline. Adverse events were reported more frequently with isosorbide dinitrate than with amlodipine (P < 0.02). Amlodipine appears to be more effective and tolerable than sustained-release isosorbide dinitrate as monotherapy for chronic stable angina.     

Cerebral circulation dysfunction and hemodynamic abnormalities in syncope during upright tilt test

OBJECTIVE: To assess the hemodynamic features, including monitoring of cerebral circulation, blood pressure and heart rate, in syncope patients during upright tilt test. DESIGN: Nonrandomized sequential patients with history of syncope of uncertain etiology compared with healthy subjects. SETTING: Noninvasive hemodynamic laboratory of a tertiary referral centre. PATIENTS: Twenty patients with history of syncope and 10 controls without syncope. PROCEDURES: Transcranial Doppler measurement or middle cerebral artery flow velocity, noninvasive and invasive blood pressure monitoring, electrocardiography and pulse oximetry monitoring during upright tilt testing. Measurements were taken in patients at the height of symptoms in supine and upright posture. MAIN RESULTS: Ten patients, while still normotensive, had a drop of 53 +/- 10% (mean +/- SD) in cerebral bloodflow velocity (P = 0.0001) and an increase in heart rate by 58 +/- 35%. The remaining 10 patients had a 58 +/- 15% reduction in cerebral bloodflow velocity (P = 0.0001), a drop in blood pressure of 33 +/- 8% (P = 0.0001) and no change in heart rate. The controls showed no significant changes in cerebral bloodflow velocity and a 25 +/- 12% increase in heart rate (P = 0.0002). CONCLUSIONS: Transcranial Doppler monitoring of cerebral bloodflow velocity during upright tilt testing may improve insight into the complex physiology of syncope.     

Hemodynamic effects of combined treatment with somatostatin analogue (SMS 201-995) and low-dose isosorbide dinitrate on portal hypertension in conscious cirrhotic rats

The authors investigated whether combined treatment with the somatostatin analogue, SMS 201-995, and low-dose isosorbide dinitrate enhanced the hemodynamic effects of the individual agents on rats with thioacetamide-induced cirrhosis. Four groups of cirrhotic rats received SMS 201-995 (0.1 microgram.min-1.kg-1), isosorbide dinitrate (10 micrograms.min-1.kg-1), both agents, or placebo, respectively. Hemodynamics were measured serially in conscious rats, using a radioactive microsphere method. SMS 201-995 reduced portal venous inflow 21 +/- 4% and portal pressure 17 +/- 3%. Isosorbide dinitrate decreased portal venous inflow 20 +/- 4%, by inducing splanchnic vasoconstriction mediated by low pressure baroreflexes, and this agent also decreased portal pressure, by 14 +/- 2%. Portal venous resistance rose 7.6 +/- 3% with isosorbide dinitrate alone, but decreased 18 +/- 4% with combination therapy. This effect may have been induced by the pronounced vasodilatory effect of isosorbide dinitrate on the venous vasculature, since the reflex splanchnic vasoconstriction that occurs with low-dose isosorbide dinitrate disappears when this agent is combined with SMS 201-995. The decrease in portal pressure was more marked (22 +/- 4%) and changes in systemic hemodynamics were milder with the combined treatment. It was concluded that combination therapy with SMS 201-995 and low-dose isosorbide dinitrate may be beneficial for portal hypertension in liver cirrhosis.     

Coronary vasoconstriction during myocardial ischemia induced by rises in metabolic demand in patients with coronary artery disease

BACKGROUND: In patients with coronary artery disease, a maximal vasodilation of the coronary microcirculation is generally assumed to occur during myocardial ischemia induced by rises in metabolic demand. However, vasoconstriction has been documented during severe prolonged ischemia in animals. The aim of this study was to investigate coronary vasomotor tone during pacing-induced ischemia in humans. METHODS AND RESULTS: The study included 11 patients with exercise-induced ischemia and single-vessel disease of the left anterior descending artery and 7 control subjects with normal coronary arteries. Blood flow velocity was monitored with a Doppler catheter in the left anterior descending artery. Coronary resistance index was calculated as the ratio between mean arterial pressure and flow velocity. Measurements were obtained at baseline, after intracoronary adenosine (2 mg), and during maximal atrial pacing in the absence and presence of adenosine. After adenosine administration at rest, coronary resistance decreased more in control subjects than in patients (25 +/- 7% of baseline versus 61 +/- 19%; P < .01). Coronary resistance decreased in all control subjects (P < .01) both at maximal pacing (60 +/- 17% of baseline) and after administration of adenosine during tachycardia (31 +/- 13% of baseline). By contrast, all 10 ischemic patients displayed increased coronary resistance at maximal heart rate (221 +/- 131% of baseline; P < .01 versus baseline, P < .01 versus control subjects). At this stage, adenosine decreased coronary resistance to 44 +/- 20% of values observed before injection. Additionally, it reduced ST-segment depression in 5 of 8 patients. CONCLUSIONS: In patients with coronary artery disease, transient myocardial ischemia induced by increased metabolic demand is not associated with maximal vasodilation. Rather, an inappropriate severe microvascular vasoconstriction is present that can be abolished by intracoronary adenosine.     

Lipopolysaccharide-neutralizing antibody reduces hepatocyte injury from acute hepatotoxin administration

OBJECTIVES: This study investigated the role of nitrate technetium-99m sestamibi imaging in predicting the postrevascularization outcome of chronically hypoperfused asynergic territories. BACKGROUND: Rest technetium-99m sestamibi myocardial scintigraphy underestimates the presence of viable myocardium in asynergic territories. Stimulation that improves coronary blood flow could increase tracer uptake in hibernating territories. METHODS: Nineteen patients with a previous myocardial infarction and left ventricular dysfunction scheduled for revascularization underwent quantitative technetium-99m sestamibi tomography under baseline conditions and during isosorbide dinitrate infusion. Global and regional function were assessed, respectively, before and after revascularization by radionuclide angiocardiography and two-dimensional echocardiography. RESULTS: Seven patients (group A) showed postrevascularization regional function recovery, and 12 (group B) showed no significant changes. In group A, nitrate infusion induced a decrease in the extent of the global uptake defect ([mean +/- SD] -37.4 +/- 21.6% of baseline value); in group B, no change or a slight increase was observed (+5.8 +/- 8.4%, p < 0.0005 vs. group A). The nitrate-induced changes in the extent of uptake defect correlated with postrevascularization changes in ejection fraction (r = -0.94, SEE 7.6). After revascularization, 11 asynergic vascular territories showed improvement (hibernating), and 34 remained unchanged (fibrotic). With administration of nitrates, 10 hibernating territories had a decrease in the extent of uptake defect, whereas only 4 of 34 of the fibrotic territories showed a nitrate-induced uptake improvement. CONCLUSIONS: Short-term administration of isosorbide dinitrate immediately before injection of technetium-99m sestamibi increases tracer uptake in some chronically hypoperfused asynergic territories. This finding correlates with the observation of post-revascularization functional recovery. Nitrate technetium-99m sestamibi myocardial scintigraphy could be a promising method for the noninvasive detection of viable hibernating myocardium.     

Effects of endothelin-1 on renal microvasculature measured using quantitative ultrasound

Renal vascular resistance is an important feature of kidney function and disease. To maintain adequate blood flow, renal vascular resistance varies in response to changes in systemic pressure. Vascular resistance is largely determined by arteriolar diameter, which is regulated by local and systemic factors. We used quantitative ultrasound techniques to follow renal vascular changes in anesthetized dogs during local intraarterial infusion of a potent vasoconstrictor, endothelin-1 (ET-1). Average arteriolar diameters were estimated by analyzing echo-signal spectra (5-15 MHz) obtained from renal cortex in vivo before, during, and after ET-1 infusion. At calculated arterial concentrations of 0.01 nM, 0.1 nM, and 1.0 nM, ET-1 reduced the average arteriolar diameter of 38 +/- 2 microns by 2%, 63%, and 91%, respectively, without producing a significant change in systemic blood pressure. Changes in scatterer size were consistent with the observed changes in renal hemodynamics detected using Doppler techniques. In addition, acoustic attenuation was found to increase with ET-1 concentration. These data suggest that quantitative ultrasound methods are sensitive to changes in renal arteriolar diameter, and may be a new noninvasive method for continuously monitoring changes in vascular resistance.     

Evaluation in vivo of the endothelial function of the native gastroepiploic artery

The endothelial function of a coronary bypass graft is an important aspect, contributing not only to its patency but to its functional performance. To evaluate this aspect in vivo, we studied 16 patients who underwent selective catheterization of the native gastroepiploic artery (GEA). Quantitative angiography of the GEA was performed at baseline, after 2 minutes' infusion of acetylcholine in three ascending doses, and after 2 mg isosorbide dinitrate injection directly into the GEA. Mean GEA diameter was 2.02 +/- 0.38 mm at baseline. We observed dose-dependent vasodilation during acetylcholine infusion: The mean diameter increased slightly to 2.11 +/- 0.32 mm (+6%, not significant) with the second dosage and, more significantly, with the highest dosage, to 2.32 +/- 0.33 mm (+18%, p < 0.001). More important vasodilation was observed after administration of nitrates (+36%, p < 0.001). We found no difference between patients with and without coronary artery disease and no relationship with risk factors for atherosclerosis. A positive correlation was seen between the vasodilation observed after nitrate administration and the highest dose of acetylcholine (r = 0.728, p = 0.002). In conclusion, the GEA demonstrates a notable vasodilatory response to nitrates (non-endothelium-dependent) and a dose-related dilator response to acetylcholine, reflecting preserved endothelial function. This sensitivity should affect favorably the hemodynamic performance of grafts performed with GEA, as well as these grafts' long-term patency rate.     

Changes in coronary vasodilation in hypertensive patients with angiographically normal coronary arteries

In normal subjects, coronary arteries dilate in response to sympathetic stimulation evoked by the cold pressor test. Similarly, in normal coronary arteries the increase in blood flow velocity induced by papaverine results in flow-dependent coronary dilation. In order to assess the coronary responses to both stimuli in hypertensive patients, variations of proximal left anterior descending coronary artery diameters and coronary blood flow velocity have been measured using quantitative coronary angiography and intracoronary Doppler in 10 control subjects and in 12 hypertensive patients. All the patients had angiographically normal coronary arteries. Total serum cholesterol, triglycerides, HDL- and LDL-cholesterol were within normal range in all patients. All patients were nonsmokers and none of them had diabetes mellitus. During the cold pressor test (hands immersed in ice water for 120 s), the rate-pressure product and coronary blood flow velocity increased respectively by 33 +/- 9% (p < 0.001) and 51 +/- 26% (p < 0.05) in control subjects, by 28 +/- 18% (p < 0.001) and 68 +/- 52% (p < 0.05) in hypertensive patients. In control subjects, coronary arteries dilated by + 12.0 +/- 4.4% (p < 0.001), and constricted by -10.3 +/- 8.5% (p < 0.001) in hypertensive patients. After injection of 10 mg of papaverine into the distal left anterior descending coronary artery, proximal left anterior descending coronary artery dilated by + 17.0 +/- 10.6% (p < 0.001) in control subjects, and did not vary (-0.7% +/- 10.6%) in hypertensive patients, when blood flow velocity was increased respectively by 449 +/- 97% and 383 +/- 103% (p < 0.001 in both groups).(ABSTRACT TRUNCATED AT 250 WORDS)     

Transmission of hepatitis C virus to infants of human immunodeficiency virus-negative intravenous drug-using mothers: rate of infection and assessment of risk factors for transmission

The acute effects of a newly synthesized thromboxane dual blocker (KDI-792), a combined thromboxane synthase inhibitor and receptor antagonist, on lower limb circulation were examined using two-dimensional color and pulse Doppler ultrasonography and laser Doppler flowmetry. A randomized single-masked, placebo-controlled trial was performed on 36 type 2 diabetic patients with minimally impaired baseline flow. The anatomical cross-sectional area (CSA), maximum flow velocity (MFV) and flow volume index (FVI) in the right dorsal pedis artery (DPA) and right femoral artery (FA) were determined by Doppler ultrasonography before and 45 and 90 minutes after the administration of either 100 or 200 mg of KDI-792 to the dose groups or placebo to the control group. Periflux blood flow (PBF) in the right foot was determined simultaneously by laser Doppler flowmetry. Both CSA and MFV in the dose groups were significantly increased in both the FA and DPA. FVI was markedly increased from 21.4 +/- 3.7 to 68.3 +/- 26.8 in the DPA (M +/- SD, P < 0.01) and from 365.4 +/- 35.3 to 771.7 +/- 75.7 in the FA (P < 0.01) in the 200 mg dose group. In the 100 mg dose group, FVI was markedly increased from 20.0 +/- 8.7 to 68.3 +/- 26.8 (P < 0.01) in the DPA and from 372.5 +/- 130.0 to 677.5 +/- 187.8 (P < 0.01) in the FA. PBF was also increased in both dose groups (from 4.15 +/- 1.4 to 7.0 +/- 4.0 ml/min/100 g tissue in the 200 mg dose group, P < 0.01), whereas there were no significant changes in either measurement in the control group. There were no significant changes in pulse rate or blood pressure after administration in either the dosage group or the placebo group. These and previous findings indicate that a single administration of KDI-792 markedly increases lower limb blood flow and might have a more potent vasodilating effect than that of prostaglandin I2 derivatives.     

Experimentally contaminated reabsorbable meshes: their evolution in abdominal wall defects

The effect of maternal hyperglycemia on fetal regional circulation in appropriate for gestational age and small for gestational age fetuses was evaluated. Color Doppler flow imaging and pulsed Doppler ultrasonographic assessments were made on 15 appropriate for gestational age and 19 small for gestational age fetuses, ranging from 33 to 40 weeks' gestation before, 60 minutes, and 120 minutes after a maternal 75 g glucose load. The pulsatility index (PI) was calculated for middle cerebral artery, descending aorta, splenic artery, renal artery, femoral artery, and umbilical artery. Simultaneously, maternal plasma glucose concentration was measured. Baseline PI value (1.50 +/- 0.31) for middle cerebral artery in small for gestational age fetuses was significantly lower than that (1.89 +/- 0.37) in appropriate for gestational age fetuses (p < 0.05); however, there were no significant differences in baseline PI values for other arteries in both groups. In appropriate for gestational age fetuses, the mean PI decreased from 1.89 +/- 0.37 to 1.47 +/- 0.33 at 60 minutes, and to 1.55 +/- 0.32 at 120 minutes (p < 0.05), but no changes were found in the other arteries. In small for gestational age fetuses, there was no significant change in PI value for each artery before and after maternal glucose load. Maternal hyperglycemia induces a significant decrease in cerebrovascular resistance in appropriate for gestational age fetuses but not in small for gestational age fetuses. These results provide a foundation for evaluating the effect of maternal hyperglycemia on fetal regional circulation.     

Experimental basis of determining maximum coronary, myocardial, and collateral blood flow by pressure measurements for assessing functional stenosis severity before and after percutaneous transluminal coronary angioplasty

BACKGROUND: Severity of coronary artery stenosis has been defined in terms of geometric dimensions, pressure gradient-flow relations, resistance to flow and coronary flow reserve, or maximum flow capacity after maximum arteriolar vasodilation. A direct relation between coronary pressure and flow, however, may only be presumed if the resistances in the coronary circulation are constant (and minimal) as theoretically is the case during maximum arteriolar vasodilation. In that case, pressure measurements theoretically can be used to predict maximum flow and assess functional stenosis severity. METHODS AND RESULTS: A theoretical model was developed for the different components of the coronary circulation, and a set of equations was derived by which the relative maximum flow or fractional flow reserve in both the stenotic epicardial artery and the myocardial vascular bed and the proportional contribution of coronary arterial and collateral flow to myocardial blood flow are calculated from measurements of arterial, distal coronary, and central venous pressures during maximum arteriolar vasodilation. To test this model, five dogs were acutely instrumented with an epicardial, coronary Doppler flow velocity transducer. Distal coronary pressures were measured by an ultrathin pressure-monitoring guide wire (0.015 in.) with minimal influence on transstenotic pressure gradient. Fractional flow reserve was calculated from the pressure measurements and compared with relative maximum coronary artery flow measured directly by the Doppler flowmeter at three different levels of arterial pressure for each of 12 different severities of stenosis at each pressure level. Relative maximum blood flow through the stenotic artery (Qs) measured directly by the Doppler flowmeter showed an excellent correlation with the pressure-derived values of Qs (r = 0.98 +/- 0.01, intercept = 0.02 +/- 0.03, slope = 0.98 +/- 0.04), of the relative maximum myocardial flow (r = 0.98 +/- 0.02, intercept = 0.26 +/- 0.07, slope = 0.73 +/- 0.08), and of the collateral blood flow (r = 0.96 +/- 0.04, intercept = 0.24 +/- 0.07, slope = -0.24 +/- 0.06). Moreover, the theoretically predicted constant relation between mean arterial pressure and coronary wedge pressure, both corrected for venous pressure, was confirmed experimentally (r = 0.97 +/- 0.03, intercept = 9.5 +/- 13.3, slope = 4.4 +/- 1.2). CONCLUSIONS: These results provide the experimental basis for determining relative maximum flow or fractional flow reserve of both the epicardial coronary artery and the myocardium, including collateral flow, from pressure measurements during maximum arteriolar vasodilation. With a suitable guide wire for reliably measuring distal coronary pressure clinically, this method may have potential applications during percutaneous transluminal coronary angioplasty for assessing changes in the functional severity of coronary artery stenoses and for estimating collateral flow achievable during occlusion of the coronary artery.     

Effect of subcutaneous administration of octreotide on endogenous vasoactive systems and renal function in cirrhotic patients with ascites

Splanchnic and systemic arteriolar vasodilation plays an important role in ascites formation in cirrhosis. Octreotide produces splanchnic vasoconstriction, but the effects on systemic hemodynamics and renal function are controversial. This study evaluated the effect of subcutaneous octreotide administration on systemic hemodynamics, endogenous vasoactive systems, and renal function in cirrhotic patients with ascites. Twenty patients were included: 10 received octreotide 250 microg/12 hr subcutaneously (for five days), and 10 did not. No statistically significant changes were found in mean arterial pressure and cardiac rate. Octreotide induced a statistically significant decrease in plasma renin activity (P < 0.01), plasma aldosterone (P = 0.01) and plasma glucagon (P < 0.05). No significant variations were observed in other systemic vasoactive substances (nitric oxide and prostacyclin). Renal function was not modified in either group. In conclusion, in cirrhotic patients with ascites, subcutaneous octreotide administration decreases plasma glucagon, renin activity, and aldosterone without changing in systemic hemodynamics or renal function.     

An anatomic study of the superficial radial nerve and its clinical implications

BACKGROUND: Acetylcholine produces coronary artery (CA) constriction in diabetic patients, suggesting an impairment of endothelium-dependent dilation. In diabetes, multiple metabolic abnormalities may inactivate nitric oxide through oxygen free radical production. METHODS AND RESULTS: To examine the mechanism of this abnormal response, two physiological tests (ie, a cold pressor test [CPT] and coronary flow increase induced by an injection of 10 mg papaverine [PAP] in the distal left anterior descending CA) were performed before and after either intravenous L-arginine (625 mg/min x 10 minutes) or intravenous deferoxamine (50 mg/min x 10 minutes) in 22 normotensive nonsmoking diabetic patients with angiographically normal CAs and normal cholesterol. Coronary surface areas were measured with quantitative angiography. Before the administration of L-arginine or deferoxamine, CPT induced CA constriction in both groups (-14 +/- 10% and -15 +/- 11%, respectively; each P<.001), and PAP injection in distal LAD did not modify significantly proximal LAD dimensions. In the 10 diabetic patients receiving L-arginine, responses to CPT and PAP were not modified. Conversely, in the 12 patients receiving deferoxamine, CA dilated in response to the two tests (+10 +/- 9% after CPT and +22 +/- 7% after PAP, each P<.001). Intracoronary isosorbide dinitrate, an endothelium-independent dilator, produced similar dilation in the two groups (+47 +/- 19% and +41 +/- 15%, respectively; each P<.001). CONCLUSIONS: This study shows that (1) responses of angiographically normal CAs to CPT and to flow increase are impaired in diabetic patients; (2) abnormal responses are not improved by L-arginine, suggesting that a deficit in substrate for nitric oxide synthesis is not involved; and (3) deferoxamine restores a vasodilator response to the two tests, suggesting that inactivation of NO by oxygen species might be partly responsible for the impairment of CA dilation in diabetic patients.     

Comparative efficacy of the intravenous administration of linsidomine, a direct nitric oxide donor, and isosorbide dinitrate in severe unstable angina. A French multicentre study. French Group of Investigators

AIMS: Although linsidomine shares common properties with nitrovasodilators, it releases nitric oxide directly without catalytic involvement by thiols. We conducted a prospective, randomized, multicentre, parallel group, single-blind study to compare the efficacy of intravenous administration of linsidomine with that of isosorbide dinitrate in unstable angina. METHODS AND RESULTS: Between November 1990 and July 1992, 568 patients with suspected unstable angina (class IIIB of the Braunwald classification) received a continuous infusion of either linsidomine (1 mg.h-1 on average) or isosorbide dinitrate (2.5 mg.h-1 on average) for 72 h. All patients received concomitant aspirin and intravenous heparin, 81% beta-blockers and 38% calcium antagonists. Holter monitoring was performed in all patients and analysed blindly. Only 25% of the patients had at least one episode of chest pain during the study (24.6% vs 25.8% in the linsidomine and isosorbide dinitrate groups, P = 0.74), of which 12% were associated with ECG changes. Holter criteria yielded similar results in both groups: 33% of patients presented episodes of myocardial ischaemia (32.6% vs 33.9% in the linsidomine and isosorbide dinitrate groups, P = 0.74), while 45% showed episodes of ventricular arrhythmia (43.5% vs 46.5% in the linsidomine and isosorbide dinitrate groups, P = 0.48). The incidence of serious clinical events at 72 h (death, myocardial infarction or myocardial revascularization) was 6.5% (5% vs 8% in the linsidomine and isosorbide dinitrate groups, P = 0.17). CONCLUSION: Intravenous linsidomine is at least as efficacious as isosorbide dinitrate in the stabilization of patients with severe unstable angina.     

Paracentesis-induced circulatory dysfunction: mechanism and effect on hepatic hemodynamics in cirrhosis

BACKGROUND & AIMS: Therapeutic paracentesis may be associated with a circulatory dysfunction, manifested by a marked increase of the plasma renin activity and plasma norepinephrine. The aim of the study was to characterize the systemic and hepatic hemodynamic changes associated with paracentesis-induced circulatory dysfunction. METHODS: Changes in plasma renin, aldosterone, and norepinephrine, and in systemic and hepatic hemodynamics were assessed 1 hour and 6 days after complete mobilization of ascites in 37 patients treated by total paracentesis plus intravenous dextran-70 infusion. RESULTS: Paracentesis-induced circulatory dysfunction occurred in 10 patients (renin and norepinephrine increased from 9.0 +/- 10.5 to 28.8 +/- 19.0 ng.mL-1.h-1 and from 752.0 +/- 364.0 to 1223.0 +/- 294.0 pg/mL, respectively) and was associated with significant reduction in systemic vascular resistance (-13.0% +/- 2.6%; P < 0.05) and increase in hepatic venous pressure gradient (from 19.5 +/- 1.5 to 22.5 +/- 2.4 mm Hg; P < 0.01). In the remaining 27 patients, mobilization of ascites also induced a significant but smaller reduction in systemic vascular resistance (-5.0% +/- 1.6%; P < 0.05) without significant changes in renin, norepinephrine, and hepatic venous pressure gradient. CONCLUSIONS: Paracentesis-induced circulatory dysfunction is predominantly caused by an accentuation of the arteriolar vasodilation already present in untreated cirrhotic patients with ascites. The homeostatic activation of endogenous vasoactive systems may account for the increased intrahepatic vascular resistance associated with this condition.     

Age-related and vasomotor stimuli-induced changes in renal vascular resistance detected by Doppler ultrasound

Indirect measurement of renal vascular resistance by duplex Doppler waveform analysis was evaluated in relation to aging and some pathophysiological conditions. Baseline renal resistive index (RRI) (peak systolic frequency shift - lowest diastolic frequency shift/peak systolic frequency shift) was measured in healthy controls aged 20 to 85 years by analyzing the blood flow velocity waveform of interlobar arteries. RRI changes induced by sympathetic activation (cold pressor test and handgrip test) or by fluid load were evaluated. Both repeatability and reproducibility were very good, as the intra and interoperator variations were all less than their reproducibility coefficients. RRI showed a significant increase with aging (ANOVA P < .001), particularly evident in subjects older than 50 years. Both the cold pressor test and handgrip test induced in all the subjects (n = 16) a significant increase in RRI (P < .001), from 0.59 +/- 0.04 to 0.69 +/- 0.04 (12 +/- 6%) for the cold pressor test and from 0.57 +/- 0.03 to 0.66 +/- 0.03 (15 +/- 2%) for the handgrip test. In eight subjects intravenous fluid load (0.25 mL/kg/min of 0.9% NaCl for 120 min) caused a significant decrease in RRI (P < .001), from 0.62 +/- 0.02 to 0.53 +/- 0.01 (17 +/- 2%), which was inversely related to mean blood pressure rise (r = 0.71, P < .001). These data show that pulsed wave Doppler analysis is an accurate method for an indirect evaluation of changes in renal vascular resistance induced by common vasomotor stimuli.     

Effects of sodium nitroprusside and phenylephrine on blood flow in free musculocutaneous flaps during general anesthesia

BACKGROUND: Hypoperfusion and necrosis in free flaps used to correct tissue defects remain important clinical problems. The authors studied the effects of two vasoactive drugs, sodium nitroprusside and phenylephrine, which are used frequently in anesthetic practice, on total blood flow and microcirculatory flow in free musculocutaneous flaps during general anesthesia. METHODS: In a porcine model (n = 9) in which clinical conditions for anesthesia and microvascular surgery were simulated, latissimus dorsi free flaps were transferred to the lower extremity. Total blood flow in the flaps was measured using ultrasound flowmetry and microcirculatory flow was measured using laser Doppler flowmetry. The effects of sodium nitroprusside and phenylephrine were studied during local infusion through the feeding artery of the flap and during systemic administration. RESULTS: Systemic sodium nitroprusside caused a 30% decrease in mean arterial pressure, but cardiac output did not change. The total flow in the flap decreased by 40% (P < 0.01), and microcirculatory flow decreased by 23% in the skin (P < 0.01) and by 30% in the muscle (P < 0.01) of the flap. Sodium nitroprusside infused locally into the flap artery increased the total flap flow by 20% (P < 0.01). Systemic phenylephrine caused a 30% increase in mean arterial pressure, whereas heart rate, cardiac output, and flap blood flow did not change. Local phenylephrine caused a 30% decrease (P < 0.01) in the total flap flow. CONCLUSIONS: Systemic phenylephrine in a dose increasing the systemic vascular resistance and arterial pressure by 30% appears to have no adverse effects on blood flow in free musculocutaneous flaps. Sodium nitroprusside, however, in a dose causing a 30% decrease in systemic vascular resistance and arterial pressure, causes a severe reduction in free flap blood flow despite maintaining cardiac output.     

Renal and hepatic nitrogen metabolism during NH4Cl ingestion in protein-deprived rats

PURPOSE: We assessed the morphodynamic features of cavernous arteries and helicine arterioles by power Doppler sonography in vasculogenic and nonvasculogenic impotent men. MATERIALS AND METHODS: A total of 40 impotent patients with and without definite vascular risk factors were studied by penile power Doppler sonography. The test was performed during penile flaccidity, after intracavernous injection of 20 mcg. alprostadil and after subsequent genital and audiovisual sexual stimulation. A second injection and stimulation were given if the erectile response observed after the initial injection was less than the maximum erection seen during sexual activity. Morphodynamic parameters evaluated by power Doppler imaging included vessel course, shape, wall thickness and pulsatility, peak systolic velocity, end diastolic velocity, acceleration time and resistance index. RESULTS: In the nonvasculogenic group all patients who achieved rigid erection showed normal cavernosal artery and helicine arteriole inflow. In these cases the arteriolar picture was characterized by the presence of 3 orders of distal ramifications originating from the cavernous arteries with an acute angle, systolic diastolic flow during penile tumescence and systolic flow alone at full rigidity. In the vasculogenic group patients with normal cavernous artery inflow showed an arteriolar tree that was pathological in 50% and was characterized by a reduced number of ramifications originating perpendicularly from the cavernous arteries and irregular caliber (arteriolar impotence). In the same group patients with reduced cavernous artery inflow also showed normal or pathological arteriolar components (pre-penile arterial impotence and diffused penile arterial impotence). CONCLUSIONS: Power Doppler sonography allows a precise study of the morphodynamics of the cavernous arteries and helicine arterioles. Our preliminary data suggest that the intracavernous arteriolar component may have a significant role in the genesis of some forms of vasculogenic impotence.     

Anti-ischemic effects of first and second dose of 20 mg isosorbide dinitrate administered 5 hours apart: attenuation of effects despite rising plasma concentration

Based on evidence that there may be early tolerance development even within the first daily cycle of treatment, this study was undertaken to evaluate the duration and extent of the antiischemic effects of two 20 mg doses of isosorbide dinitrate as used in a well-established regimen documented to maintain effectiveness during long-term treatment. Ischemia parameters were analyzed at 2 and 4 1/2 hours after the first dose as well as at 2 and 7 hours after the second dose given 5 hours later. The studies were performed in 10 male patients with documented coronary artery disease using bicycle ergometry and a double-blind, randomized, placebo-controlled, crossover protocol. ST-segment depression was reduced by 59% (p < 0.0005) at 2 hours and by 42% (p < 0.01) at 4 1/2 hours after the first tablet and by 38% (p < 0.005) at 2 hours and by 15% (p < 0.05) at 7 hours after the second tablet. Increments in ischemia-free workload capacity amounted to 112% (p < 0.005) and to 41% (p < 0.05) after the first tablet and 68% (p < 0.05) and 38% (p < 0.05) at 2 and 7 hours after the second tablet. At 2 and 4 1/2 hours after the first tablet, plasma concentrations of isosorbide dinitrate were 8.4 and 5.9 ng/ml, and those of isosorbide-5-mononitrate were 166.6 and 130.3 ng/ml. At 2 and 7 hours after the second tablet, the concentrations of isosorbide dinitrate were 9.1 and 5.9 ng/ml, and those of isosorbide-5-mononitrate were 224.5 and 148.1 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sardinian alcohol-preferring rats prefer chocolate and sucrose over ethanol

The purpose of this study was to evaluate the effect of sequential external counterpulsation (SECP) on cerebral and renal blood flow. The effect of SECP on carotid and renal artery blood flow was studied in 35 and 18 patients, respectively. With a portable unit, cuffs were applied to the calves and thighs, sequentially inflated with air at the onset of diastole, and deflated at the onset of systole. Carotid and renal artery Duplex studies were performed during intermittent SECP. Flow velocity and flow velocity integral were measured at baseline and during SECP. Diastolic augmentation of carotid and renal artery flow velocity was observed in all patients. The mean carotid flow velocity integral increased by 22% from 27.7 +/- 1.8 cm to 33.1 +/- 2.3 cm (P = 0.001). The mean renal artery flow velocity integral increased by 19% from 21 +/- 1 cm to 25 +/- 1 cm (P = 0.0001). With SECP, a new diastolic Doppler flow velocity wave was observed, with an average peak carotid diastolic flow velocity of 56 +/- 4 cm/sec and an average peak renal artery diastolic flow velocity of 40 +/- 2.5 cm/sec. This diastolic wave was 75% (carotid) and 68% (renal) as high as the systolic wave during SECP. In addition, with SECP the systolic wave increased by 6% and 8% in the carotid and renal artery, respectively (P = 0.02 and 0.006, respectively). In conclusion, SECP significantly increases carotid and renal blood flow. This noninvasive, harmless treatment may be useful to support patients with decreased cerebral and renal perfusion.