An association study between a transcriptional polymorphism in the serotonin transporter gene and panic disorder in a Japanese population

1. To determine the effects of an acute oral dose of glibenclamide on blood pressure (BP), basal forearm vascular resistance (FVR) and FVR responses to the K+ATP channel activating vasodilator diazoxide, a placebo-controlled, double-blind cross-over study was performed in eight male volunteers with non-insulin-dependent diabetes mellitus. 2. Changes in vascular responses to progressively increasing concentrations of diazoxide (3.75-30 mg/kg per min) and noradrenaline (25-100 ng/kg per min) were measured by venous occlusion plethysmography. 3. Glibenclamide significantly lowered plasma glucose levels compared with placebo (P < 0.02) and attenuated the decrease in FVR (P < 0.05) and the decrease in systolic BP (P < 0.05) that followed a meal. However, vasodilator responses to diazoxide were potentiated by the administration of oral glibenclamide (P < 0.01). 4. Acute administration of oral glibenclamide attenuates the normal decrease in FVR and systolic BP that follows a meal and potentiates rather than inhibits forearm vasodilator responses to intra-arterial diazoxide, probably via indirect humoral effects. These results suggest that glibenclamide has direct or indirect vasoconstrictor effects that antagonize the normal increase in forearm blood flow that follows a meal and that the inhibition of vascular K+ATP channels following acute oral glibenclamide administration is clinically insignificant compared with other indirect vascular effects of the drug.     

Effect of diaspirin cross-linked hemoglobin and norepinephrine on systemic hemodynamics and regional circulation in rats

Diaspirin cross-linked hemoglobin (DCLHb) (400 mg/kg, i.v.) produced a pressor effect that was equal to that produced by norepinephrine (NE) (25 micrograms/kg/min i.v. infusion). Total peripheral resistance was increased by DCLHb and more significantly by NE. Heart rate was not affected by DCLHb but was significantly increased by NE. The cardiac output and stroke volume were insignificantly increased by DCLHb but were significantly decreased by NE. DCLHb and NE produced a significant increase in blood flow to the heart. The vascular resistance in the heart was not affected by DCLHb but was decreased by NE. DCLHb did not affect the renal and brain circulation, but NE in kidneys decreased the blood flow and increased the vascular resistance, whereas in the brain it increased the blood flow and decreased the vascular resistance. DCLHb increased the blood flow to the stomach and small intestine. The vascular resistance was not affected by DCLHb in the gastrointestinal tract. NE did not affect the blood circulation in the gastrointestinal tract. Blood flow to the spleen was increased by DCLHb, and there was no change in the vascular resistance. NE insignificantly decreased the blood flow to the spleen and significantly increased the vascular resistance. The blood circulation to the mesentery and pancreas was not affected by DCLHb, whereas NE increased the blood flow without affecting the vascular resistance. DCLHb produced a significant increase in the blood flow to the skin without affecting the vascular resistance, whereas NE did not affect the blood flow but increased the vascular resistance. DCLHb did not affect the blood flow to the musculo-skeletal system but increased the vascular resistance, whereas NE decreased the blood flow and increased the vascular resistance. In summary, although the pressor effect of DCLHb and NE at the doses studied is equal, DCLHb did not decrease the blood flow to any organ, whereas NE produced significant decreases in blood flow to several organs. It is concluded that the blood flow to most of the organs is either increased or not affected by DCLHb.     

Effects of continuous infusion of endothelin-1 in pregnant sheep

Plasma concentration of endothelin-1, a potent vasoconstrictor produced by the vascular endothelium, has been observed to be significantly increased in a number of pathophysiological states, including preeclampsia. In the present study we have evaluated the effects of elevated plasma endothelin-1 in pregnant sheep by continuous exogenous endothelin-1 administration. Nine pregnant ewes (110+/-5 days' gestation) were instrumented for measurements of maternal mean arterial pressure, renal blood flow, and uterine blood flow. After recovery, endothelin-1 was infused intravenously for 4 hours at a dose that was adjusted to raise mean arterial pressure by approximately 20 mm Hg by the end of the first hour (range 5 to 20 ng/kg per minute). Mean arterial pressure, renal blood flow, uterine blood flow, urinary protein excretion, hematocrit, and plasma endothelin-1 concentration were measured hourly, and renal and uterine vascular resistances were calculated. Endothelin-1 produced significant increases (% change from baseline at t=4 hours) in mean arterial pressure (45+/-8%), renal vascular resistance (353+/-66 %), and uterine vascular resistance (59+/-21%). Endothelin-1 also increased microvascular permeability both systemically and within the kidney, as suggested by marked increases in hematocrit (0.27+/-0.01 to 0.32+/-0.01) and urinary protein concentration (0.95+/-0.1 to 7.9+/-3.2 mg/mL per mg creatinine). There was a highly significant correlation (P<.0001) between plasma endothelin-1 and mean arterial pressure, renal vascular resistance, uterine vascular resistance, hematocrit, and urinary protein content in all sheep studied. In addition, plasma endothelin-1 corresponded well with the time course of the changes in cardiovascular parameters and urinary protein excretion observed. These results provide evidence to suggest that elevation of circulating endothelin-1 in pregnant sheep can produce cardiovascular and hemodynamic changes that in many ways resemble the human disease preeclampsia. This supports the hypothesis that endothelial cell damage and/or dysfunction that is associated with increased production of endothelin-1 could directly contribute to the progression of preeclampsia.     

Effect of prostaglandins on vascular resistance and adrenergic vasoconstrictor responses in the canine uterus

Prostaglandins appear to play an important role in a number of reproductive processes. The effect of prostaglandins on numerous vascular beds has been extensively studied, but the effects on uterine hemodynamics have not. The present study was designed to determine the effects of prostaglandins of the A and E series on uterine vascular resistance and responses to adrenergic nerve stimulation in the canine uterus. PGE1, PGE2 and PGA1 were found to be potent uterine vasodilators. In addition, these agents were able to modify adrenergic vasoconstrictor responses. These effects on uterine vascular resistance and adrenergic vasoconstrictor responses were separable. The results of these studies suggest that prostaglandins of the A and E series may play an important role in regulating uterine blood flow in the nonpregnant animal.     

The effectiveness of hospital at home compared with in-patient hospital care: a systematic review

As nitric oxide (NO) may be a particularly important vasodilator in early life, we investigated its role in the regulation of the gastrointestinal (GI) circulation at mid-gestation. Cardiac output and GI blood flow were measured by the radioactive microsphere technique in eight chronically instrumented and unanesthetized mid-gestation fetal sheep. Mean arterial pressure (MAP), heart rate, blood flow, oxygen delivery, and vascular resistance were determined before and after infusion of the specific NO synthase inhibitor, Nomega-nitro-L-arginine (L-NNA) at doses of 10 and 25 mg/kg. In response to L-NNA infusion, MAP increased (p < 0.01) and combined ventricular output decreased (p < 0.001). GI blood flow and oxygen delivery decreased and vascular resistance increased in the stomach and all segments of the small and large intestine (all p < 0.001). The greatest reduction in blood flow was in the small intestine (p < 0.01) and the basal differential pattern of small intestinal blood flow exceeding large intestinal flow was completely abolished. These changes were much greater than those previously described in late-gestation fetuses. Our results suggest that, at mid-gestation, NO plays a major role in the regulation of blood flow and vascular tone across all segments of the fetal GI tract, with its effects being more pronounced than later in development.     

Scotophase-dependent thermoregulatory dysfunction in pinealectomized chickens

The effect of induced maternal hyperthermia (1.5 degrees C rise over 60 min) on the uterine and umbilical circulations was examined in two groups of chronically instrumented pregnant sheep. Hyperventilation occurred in both groups. In the group in which the resultant respiratory alkalosis was untreated (N = 5), uterine blood flow decreased to 53 +/- 3% (mean +/- SE; P less than 0.01) of control at maximal maternal temperature. Umbilical blood flow also decreased 30 +/- 6% (P less than 0.01) below control levels. In the other group, normocapnia was maintained (N = 4). Uterine blood flow decreased in this group to 75% +/- 2% (P less than 0.01) of control levels, but umbilical blood flow did not significantly change. There was no significant change in maternal or fetal mean arterial pressure during hyperthermia in either group. Thus, maternal hyperthermia per se results in a significant decrease in uterine blood flow primarily through an effect on uterine vascular resistance, but without a concomitant change in umbilical blood flow.     

Cloning of Drosophila MCM homologs and analysis of their requirement during embryogenesis

Modification of blood flow by endothelin-1 (ET-1) was examined in the s.c. HSN fibrosarcoma and compared to normal tissues of anaesthetised CBH/CBi rats. The ET receptor subtypes involved in the response were investigated using the ET(A) and ET(B) receptor antagonists BQ-610 and BQ-788, respectively. Blood flow and vascular resistance were determined using the uptake of radiolabelled iodo-antipyrine (125I-IAP). BQ-610 or BQ-788 was infused for 30 min prior to blood flow determination. ET-1 was administered 15 min into the infusion time. BQ-610 and BQ-788 infused alone did not modify any vascular parameters. Tumour blood flow increased slightly following ET-1, contrasting with most normal tissues, in which blood flow was reduced. Vascular resistance increased in all tissues, including the tumour. Neither antagonist significantly modified the ET-1-induced changes in tumour blood flow or vascular resistance, whereas in the majority of normal tissues BQ-610 attenuated and BQ-788 potentiated the vascular resonse to ET-1. Our results show that the HSN tumour vasculature is only weakly responsive to ET- 1 and antagonism of its effects by BQ-610 and BQ-788. This contrasts with the majority of normal tissues, in which ET- 1 induces an intense vasoconstriction.     

Hemodynamic factors affecting uterine artery Doppler waveform pulsatility in sheep

Quantitative analysis of vascular resistance from the Doppler time-velocity waveform relies on measuring arterial pulsatility. However, input pressure waveform pulsatility, impedance, and resistance have all been found to effect artery flow waveform pulsatility in circulatory mathematic models and in umbilical sheep preparations in vivo. The present study used an in vivo sheep preparation to determine that embolization of the uteroplacental circulation and maternal angiotensin II administration caused changes in the uterine Doppler time-velocity waveform pulsatility that were dependent on input pressure waveform pulsatility, fundamental impedance, and resistance changes. Uteroplacental vascular embolization increased vascular resistance and the uterine artery Doppler waveform resistive index; the mean component of flow (mean pressure/resistance) decreased. Decreased uterine artery Doppler resistive index occurred despite angiotensin II-induced vasoconstriction and increased vascular resistance because the pulse component of flow (pulse pressure/impedance) decreased.     

Effects of etomidate administration on cerebral collateral flow

OBJECTIVE: Augmentation of blood flow to collateral-dependent tissue (CDT) as a result of selective vasodilation of collateral vessels has been shown to occur with various stimuli after middle cerebral artery occlusion. Etomidate, a carboxylated imidazole derivative, is a nonbarbiturate anesthetic that is used clinically both as an anesthetic and as a neuroprotective agent. The effect etomidate has on collateral cerebral vessels is unknown. The purpose of our studies was to test whether etomidate selectively augmented cerebral blood flow (CBF) to CDT during ischemia as an additional mechanism of neuroprotection. METHODS: A left craniotomy was performed in each of 14 dogs, with the animals under halothane anesthesia. A branch of the middle cerebral artery was occluded and cannulated distally for determination of CDT using a "shadow flow" technique. CBF and vascular pressures were measured and used to calculate vascular resistance. An etomidate infusion (0.1 mg/kg of body weight/min administered intravenously) was started, and CBF and vascular pressures were measured at 10 and 40 minutes. Hypotension was then induced, and CBF and pressures were again measured. RESULTS: CBF was significantly reduced in all regions of the brain, including CDT, when etomidate was infused. CDT showed a 53.7% reduction in flow, whereas normal CBF was reduced by at least 63.4%. During hypotension, blood flow to CDT was reduced by an additional 42.7%, whereas normal cerebrum was reduced by at least 22.7%. Vascular resistance was increased in all vessels during etomidate infusion. CONCLUSION: The neuroprotective effects of etomidate do not seem to be through the augmentation of collateral or global CBF.     

Gait patterns in children with hemiplegic spastic cerebral palsy

Our objective was to study uterine and umbilical artery flow resistance during the oxytocin challenge test (OCT). The study population was 21 women with suspected placental insufficiency; one woman was excluded because of a positive OCT with reactive fetal heart rate pattern. We carried out simultaneous electronic fetal heart rate monitoring and Doppler velocimetry of uterine and umbilical artery flow during the OCT. The uterine artery flow resistance increased significantly during contractions in both OCT-positive (n = 5) and OCT-negative (n = 15) cases compared with basal values, but the increase was significantly higher in positive cases. The umbilical artery flow resistance increased significantly during contractions in OCT-positive cases, but was almost unchanged in negative cases. During uterine inactivity, there were no differences between the groups for any vessel. This study showed that fetal heart rate decelerations during the OCT are associated with rapid and exaggerated increases of vascular resistance in both uterine and umbilical arteries. The causal relationship is unknown, but the findings indicate pathophysiological mechanisms revealed only during uterine contractions.     

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.     

Gross efficiency of muscular work during step exercise at -15 degrees C and 21 degrees C

The systemic and regional hemodynamic effects of inhibition of endothelium-derived relaxing factor/nitric oxide (EDRF/NO) were studied in awake, indomethacin-treated rats. The radiolabeled microsphere method was used to determine the cardiac output, systemic vascular resistance (SVR), and regional blood flows and regional vascular resistances in 12 tissues before and after infusion of the EDRF/NO synthesis inhibitor, NG-monomethyl-L-arginine (NMMA, 100 mg/kg), and after reversal of NMMA by infusion of L-arginine (300 mg/kg). NMMA infusion resulted in increases in the blood pressure and SVR. After NMMA, blood flows were decreased to the cerebrum, heart, kidney, spleen, gastrointestinal tract, skin, ear, and white fat, whereas flow in the hepatic artery was increased. Vascular resistances were increased in every tissue studied except the hepatic artery, in which the resistance decreased after NMMA. L-arginine restored the vascular resistance to control values in 8 of the 12 tissues. The magnitude of the increase in the regional resistance was not uniform among the organs studied, and ranged from a maximum of 253% in brown fat to 22% in heart. These results indicate that EDRF/NO is an important mediator of regional hemodynamic control in numerous tissues of the intact rat. The marked heterogeneity in the magnitude of basal EDRF/NO-dependent tone suggests that the mechanisms mediating this cardiovascular control system are regulated locally.     

Quality of life assessment in reflux disease

It has been suggested that inhibitors of nitric oxide synthesis are of value in the treatment of hypotension during sepsis. In this pilot study, we examined the effects of inhibition of nitric oxide synthesis by continuous infusion of N(omega)-nitro-L-arginine methyl ester (L-NAME) at 1.5 mg/kg/h in a patient with severe septic shock. L-NAME produced a rise in mean arterial blood pressure and systemic vascular resistance; catecholamine infusion could be reduced. Parallel to these findings, there was a 50% reduction in cardiac output and a 5-fold rise in pulmonary vascular resistance, which resulted in severe pulmonary hypertension after 3 h of L-NAME infusion, for which the infusion had to be stopped. Following the termination of L-NAME infusion, pulmonary artery pressure and blood pressure returned to baseline values, although pulmonary and systemic vascular resistance remained elevated for several hours. We conclude that nitric oxide appears to play a role in the cardiovascular derangements during human sepsis. Inhibition of nitric oxide synthesis with L-NAME can increase blood pressure and systemic vascular resistance. However, reduced cardiac output and pulmonary hypertension are possible side effects of continuous NO synthase inhibition. These side effects necessitate careful monitoring and may hinder the clinical application of NO synthase inhibitors.     

Cholera toxin acts as a potent adjuvant for the induction of cytotoxic T-lymphocyte responses with non-replicating antigens

OBJECTIVE: To evaluate the relation between the development of the uteroplacental circulation as assessed by Doppler velocimetry and the maternal blood relaxin concentration. METHODS: Transvaginal color Doppler investigation of the uteroplacental circulation was performed in 42 healthy women at 6-15 weeks' gestation before termination of pregnancy for psychosocial reasons. The resistance index (RI), pulsatility index (PI), and maximum peak velocity were recorded at the level of the main uterine artery, and the presence of intervillous flow was noted. Relaxin, hCG, 17 beta-estradiol (E2), and progesterone levels were measured in maternal venous blood. RESULTS: Limited intervillous flow was noted from 10 weeks' gestation and continuous intervillous flow from 12 weeks. An inverse relation was observed between the circulating levels of both E2 and progesterone and uterine artery RI and PI, whereas the relaxin level correlated positively with uterine RI and PI. Estradiol and progesterone levels also correlated positively with uterine peak systolic velocity and intervillous blood flow. Multiple linear regression analysis indicated that both hormones contributed to the decrease in downstream resistance to uterine blood flow with advancing gestational age, as assessed by uterine RI. In addition, relaxin contributed to the uterine RI and PI and to the intervillous blood flow. CONCLUSION: These data suggest that relaxin, E2, and progesterone may influence the changes in uterine blood flow that occur in early pregnancy. The role played by E2 and progesterone in the development of the uteroplacental circulation may be modulated by relaxin, constituting a novel function for this ovarian peptide.     

Interphase cytogenetics and competitive RT-PCR for residual disease monitoring in patients with chronic myeloid leukaemia during interferon-alpha therapy

OBJECTIVES: We sought to determine whether the antioxidant vitamin C improves endothelium-dependent vasodilation of forearm resistance vessels in patients with insulin-dependent diabetes mellitus. BACKGROUND: Endothelium-dependent vasodilation is impaired in patients with diabetes mellitus. Oxidatively mediated degradation of endothelium-derived nitric oxide contributes to abnormal endothelium-dependent vasodilation in animal models of diabetes mellitus. METHODS: The study group included 10 patients with insulin-dependent diabetes mellitus and 10 age-matched control subjects. Forearm blood flow was determined by venous occlusion plethysmography. Endothelium-dependent vasodilation was assessed by intraarterial infusion of methacholine (0.3 to 10 microg/min). Endothelium-independent vasodilation was assessed by intraarterial infusion of nitroprusside (0.3 to 10 microg/min). Forearm blood flow dose-response curves were determined for each drug infusion before and during concomitant infusion of vitamin C (24 mg/min). RESULTS: In diabetic subjects, endothelium-dependent vasodilation was augmented by the concomitant infusion of vitamin C (p = 0.001). Endothelium-independent vasodilation was not affected by the concomitant infusion of vitamin C (p = NS). In control subjects, vitamin C infusion did not affect endothelium-dependent vasodilation (p = NS). CONCLUSIONS: Vitamin C selectively restores the impaired endothelium-dependent vasodilation in the forearm resistance vessels of patients with insulin-dependent diabetes mellitus. These findings indicate that nitric oxide degradation by oxygen-derived free radicals contributes to abnormal vascular reactivity in humans with insulin-dependent diabetes mellitus.     

Changes in cerebral perfusion pressure in puerperal women with preeclampsia

OBJECTIVE: To determine the variation in the estimated maternal cerebral perfusion and cerebrovascular resistance (the resistance area product) in the puerperium. METHODS: The maternal middle cerebral artery was evaluated by transcranial Doppler ultrasound in ten women 2 days before labor, in 21 women in early labor and at 24 and 48 hours postpartum, and in 6 women at 1 week postpartum. Cerebral blood flow velocities were determined. Women were diagnosed initially with mild preeclampsia. Estimated cerebral perfusion pressure was Vmean/[Vmean - Vdiastolic] [BPmean - BPdiastolic]. Because the diameter of the vessels could not be measured directly, an index of resistance was calculated: the resistance area product = BPmean/velocitymean. We calculated an index of cerebral blood flow to be estimated cerebral perfusion pressure divided by resistance area product. Our study had a power of 80% to detect a 16-cm/second increase in middle cerebral blood flow velocity. RESULTS: Estimated maternal cerebral perfusion was maintained for up to 1 week postpartum. Cerebrovascular resistance did not change in the puerperium. Cerebral blood flow index (+/-standard deviation) was significantly increased at 1 week postpartum compared with early labor levels (28.3 +/-6.9 versus 46.7+/-15.6, respectively) (P < .05). CONCLUSION: Cerebral blood flow 1 week postpartum increased significantly over early labor values. These persistent changes in the cerebral vasculature might put patients at risk for seizures up to 1 week postpartum.     

Effects of magnesium sulphate on the noradrenaline-induced cerebral vasoconstrictor and pressor responses in the goat

OBJECTIVE: To examine the ability of magnesium sulphate to counteract the noradrenaline-induced cerebral vasoconstrictor and pressor responses in goats by using both in vivo and in vitro techniques. DESIGN: Cerebral blood flow was measured in vivo by means of an electromagnetic flow probe around the internal maxillary artery. Isometric tension was recorded in vitro from rings of goat middle cerebral artery maintained in an organ bath. RESULTS: 1. In vivo. Continuous infusion of noradrenaline (10 micrograms/min) directly into the cerebral arterial supply elicited sustained decrease in cerebral blood flow (61% [SEM 3] of control values) and increase in cerebral vascular resistance (178% [SEM 9] of control values). Magnesium sulphate, injected directly into the cerebral arterial supply (10-300 mg) or infused intravenously (0.3 g and 3 g during 15 min) at the noradrenaline-induced steady state, increased cerebral blood flow by decreasing cerebral vascular resistance in a dose-dependent manner. A similar result was obtained when intravenous magnesium sulphate (3 g/15 min) was tested against the cerebral vasoconstrictor and pressor responses induced by intravenous infusion of noradrenaline (30 micrograms/min). 2. In vitro. When compared with the response obtained in a control medium (1 mmol/L Mg2+), 10 mmol/L Mg2+ significantly inhibited the maximum contraction elicited by noradrenaline (10(-8) to 3 x 10(-3) mol/L) from 45% [SEM 4] to 26% [SEM 4]. CONCLUSIONS: Magnesium sulphate reverses the noradrenaline-induced cerebral vasoconstrictor and pressor responses by a direct inhibitory action of Mg2+ on the actions of noradrenaline in the cerebral and peripheral vascular beds, which leads to a decrease in vascular resistance. These results could explain, at least in part, the beneficial effects of magnesium sulphate in the management of preeclampsia and eclampsia.     

Effect of antenatal administration of thyrotrophin releasing hormone on fetal flow velocity waveforms

AIM: To determine whether antenatal administration of thyrotrophin releasing hormone (TRH), to promote lung maturation, alters blood flow through the fetal middle cerebral, umbilical artery, or ductus arteriosus and through the maternal uterine arteries. METHODS: The effect of transplacentally administered TRH on the fetal circulation was prospectively evaluated in 30 patients between 24 and 34 weeks' gestation. TRH (400 micrograms) was given to the mother intravenously either as a bolus or an infusion. Fetal effects were determined by measuring the maximum velocity and pulsatility index (PI) in middle cerebral artery, ductus arteriosus, uterine artery and umbilical artery Doppler waveforms. Measurements were made immediately before, and 10 and 60 minutes after maternal TRH administration. RESULTS: Intravenous injection of TRH had no significant effect on PI in the uterine, umbilical, or middle cerebral artery and the ductus arteriosus within 60 minutes of administration in either group. CONCLUSION: The antenatal use of TRH in conjunction with steroids for fetal lung maturity does not affect utero-placental or fetal haemodynamic variables, as measured by Doppler. These findings, therefore, do not support the suggestion that antenatal intravenous administration of TRH either as bolus or infusion may have immediate adverse vascular effects in the fetus.     

Milrinone improves pulmonary hemodynamics and right ventricular function in chronic pulmonary hypertension

BACKGROUND: Right ventricular failure after cardiac transplantation is commonly related to preexisting recipient pulmonary hypertension. This study was designed to investigate the effects of intravenous milrinone on pulmonary hemodynamic indices and right ventricular function in a canine model of monocrotaline pyrrole-induced chronic pulmonary hypertension. METHODS: Eight mongrel dogs underwent pulmonary artery catheterization to measure right-sided hemodynamic indices before and 6 weeks after a right atrial injection of monocrotaline pyrrole. Six weeks after injection, all hearts were instrumented with a pulmonary artery flow probe, ultrasonic dimension transducers, and micromanometers. Data were collected at baseline and after milrinone infusion. RESULTS: Six weeks after monocrotaline pyrrole injection, significant increases in the pulmonary artery pressure and pulmonary vascular resistance were observed. Milrinone led to significant increases in right ventricular function as well as significant improvements in pulmonary vascular resistance, pulmonary blood flow, and left ventricular filling. CONCLUSIONS: This investigation demonstrates the well-known hemodynamic and inotropic effects of milrinone which, in the setting of monocrotaline pyrrole-induced pulmonary hypertension, were also associated with significant increases in pulmonary blood flow and left ventricular filling.     

Insulin and amino acid infusion after cardiac operations: effects on systemic and renal perfusion

OBJECTIVE: The purpose of this study was to answer two questions: (1) Does a mixed amino acid infusion enhance systemic and renal perfusion in the early postoperative period after heart operations? (2) Does the addition of insulin (glucose-insulin-potassium solution) provide additional effects to those of an amino acid infusion? METHODS: Thirty-three male patients undergoing coronary artery bypass grafting (mean age 65.9 +/- 1.2 years) were included in a prospective, controlled, randomized study. Eleven patients (AA group) received infusion of mixed amino acids (11.4 gm), 11 patients (AA + GIK group) received infusion of mixed amino acids (11.4 gm) and insulin solution (225 IU insulin, glucose with glucose clamp technique, and potassium), and 11 patients served as control subjects. RESULTS: Amino acid infusion alone had no effect on systemic vascular resistance or cardiac index but increased renal blood flow 51% +/- 11% (from 114 +/- 13 to 172 +/- 24 ml.min-1.m-2 in one kidney, p < 0.05 vs the control group). Insulin solution in addition to amino acid infusion reduced systemic vascular resistance 24% +/- 3% (from 1280 +/- 85 to 960 +/- 57 dyn.sec.cm-5, p < 0.05 vs the control and AA groups) and increased cardiac index 13% +/- 3% (from 2.3 +/- 0.2 to 2.6 +/- 0.2 L.min-1.m-2, p < 0.05 vs the control and AA groups). Insulin had no significant additive effect on renal blood flow. CONCLUSIONS: Our data imply that (1) infusion of mixed amino acids enhances renal blood flow after cardiac operations but has no effect on systemic perfusion and (2) the addition of insulin solution improves systemic perfusion. The combined treatment may potentially reduce the risk of renal hypoperfusion injury in the postoperative period after coronary artery bypass grafting.