Increase In Aortic Blood Flow Research Articles

Selepressin and Arginine Vasopressin Do Not Display Cardiovascular Risk in Atherosclerotic Rabbit.

BackgroundSeptic shock remains associated with significant mortality rates. Arginine vasopressin (AVP) and analogs with V1A receptor agonist activity are increasingly used to treat fluid-resistant vasodilatory hypotension, including catecholamine-refractory septic shock. Clinical studies have been restricted to healthy volunteers and catecholamine-refractory septic shock patients excluding subjects with cardiac co-morbidities because of presumed safety issues. The novel selective V1A receptor agonist selepressin, with short half-life, has been designed to avoid V2 receptor-related complications and long-term V1A receptor activation. Cardiovascular safety of selepressin, AVP, and the septic shock standard of care norepinephrine was investigated in a rabbit model of early-stage atherosclerosis.MethodsAtherosclerosis was established in New Zealand White rabbits using a 1% cholesterol-containing diet. Selepressin, AVP, or norepinephrine was administered as cumulative intravenous infusion rates to atherosclerotic and non-atherosclerotic animals.ResultsSelepressin and AVP induced a slight dose-dependent increase in arterial pressure (AP) associated with a moderate decrease in heart rate, no change in stroke volume, and a moderate decrease in aortic blood flow (ABF). In contrast, norepinephrine induced a marked dose-dependent increase in AP associated with a lesser decrease in the heart rate, an increase in stroke volume, and a moderate increase in ABF. For all three vasopressors, there was no difference in responses between atherosclerotic and non-atherosclerotic animals.ConclusionFurther studies should be considered using more advanced atherosclerosis models, including with septic shock, before considering septic shock clinical trials of patients with comorbidities. Here, selepressin and AVP treatments did not display relevant cardiovascular risk in early-stage rabbit atherosclerosis.

The Utility of Aortic Blood Flow Measurements in the Prediction of Pulmonary Artery Banding Outcome

The purpose of this study was to evaluate the clinical utility of intraoperative aortic blood flow measurements on clinical outcome in patients undergoing pulmonary artery banding (PAB). We reviewed 12 patients who underwent a PAB between September 2008 and March 2013 who also had intraoperative aortic blood flow measurements. Diagnosis included biventricular physiology in 6, single-ventricle physiology in 4, and inadequate systemic ventricle in 2 patients. Aortic blood flow was measured at the time of surgery by Transonic flow probe (Transonic Systems Inc, Ithaca, NY). Aortic flow, intraoperative hemodynamics, and clinical outcomes were analyzed to determine the potential predictive utility of intraoperative variables on postoperative outcomes. The aortic flow increased after PAB from 1.56 ± 0.73 to 2.20 ± 1.10 L · min(-1) · m(-2) (41.0% increase; p= 0.001). The efficacy of the PAB procedure was found to bedirectly related to the percentage increase in aortic blood flow measured intraoperatively. Three patients with lessthan 20% increase in aortic blood flow died, required re-PAB, or developed ventricular dysfunction, while patients with successful PAB had more than 40% increase in aortic blood flow. The percentage increase inaortic blood flow was not predictable based on pre-band or post-band absolute aortic blood flow measurements. Thepercentage increase in aortic blood flow was inversely correlated to the tightness of the PAB as defined relative to that predicted by the Trusler formula (r= 0.67; p= 0.01). This study identifies the change in the aortic blood flow as a new, physiologically based parameter to help predict PAB outcome.

Renal Perfusion Assessment by Renal Doppler During Fluid Challenge in Sepsis

To assess renal resistive index variations in response to fluid challenge. Prospective cohort study. Three ICUs in French teaching hospitals. Consecutive patients receiving mechanical ventilation and requiring a fluid challenge. Resistive index measurement before and after fluid challenge. Renal Doppler was used to measure resistive index and esophageal Doppler to monitor aortic blood flow. Of the 35 included patients, 17 (49%) met our definition for fluid challenge responsiveness, that is, had at least a 10% increase in aortic blood flow. After fluid challenge, mean arterial pressure increased from 73 mm Hg (interquartile range 68-79) to 80 mm Hg (75-86; p < 0.0001) and stroke volume from 50 mL (30-77) to 55 mL (39-84; p < 0.0001). Stroke volume changes after fluid challenge were +28.6% (+18.8% to +38.8%) in fluid challenge responders and +3.1% (-1.6% to 7.4%) in fluid challenge nonresponders. Renal resistive index was unchanged after fluid challenge in both nonresponders (0.72 [0.67-0.75] before and 0.71 [0.67-0.75] after fluid challenge; p = 0.62) and responders (0.70 [0.65-0.75] before and 0.72 [0.68-0.74] after fluid challenge; p = 0.11). Stroke volume showed no correlations with resistive index changes after fluid challenge in the overall population (r² = 0.04, p = 0.25), in fluid challenge responders (r² = -0.02, p = 0.61), or in fluid challenge nonresponders (r² = 0.08, p = 0.27). Stroke volume did not correlate with resistive index changes after fluid challenge in the subgroups without acute kidney injury (AKIN definition), with transient acute kidney injury, or with persistent acute kidney injury. Systemic hemodynamic changes induced by fluid challenge do not translate into resistive index variations in patients without acute kidney injury, with transient acute kidney injury, or with persistent acute kidney injury.

An Increase in Aortic Blood Flow after an Infusion of 100 ml Colloid over 1 Minute Can Predict Fluid Responsiveness

Predicting fluid responsiveness remains a difficult question in hemodynamically unstable patients. The author's objective was to test whether noninvasive assessment by transthoracic echocardiography of subaortic velocity time index (VTI) variation after a low volume of fluid infusion (100 ml hydroxyethyl starch) can predict fluid responsiveness. Thirty-nine critically ill ventilated and sedated patients with acute circulatory failure were prospectively studied. Subaortic VTI was measured by transthoracic echocardiography before fluid infusion (baseline), after 100 ml hydroxyethyl starch infusion over 1 min, and after an additional infusion of 400 ml hydroxyethyl starch over 14 min. The authors measured the variation of VTI after 100 ml fluid (ΔVTI 100) for each patient. Receiver operating characteristic curves were generated for (ΔVTI 100). When available, receiver operating characteristic curves also were generated for pulse pressure variation and central venous pressure. After 500 ml volume expansion, VTI increased ≥ 15% in 21 patients (54%) defined as responders. ΔVTI 100 ≥ 10% predicted fluid responsiveness with a sensitivity and specificity of 95% and 78%, respectively. The area under the receiver operating characteristic curves of ΔVTI 100 was 0.92 (95% CI: 0.78-0.98). In 29 patients, pulse pressure variation and central venous pressure also were available. In this subgroup of patients, the area under the receiver operating characteristic curves for ΔVTI 100, pulse pressure variation, and central venous pressure were 0.90 (95% CI: 0.74-0.98, P < 0.05), 0.55 (95% CI: 0.35-0.73, NS), and 0.61 (95% CI: 0.41-0.79, NS), respectively. In patients with low volume mechanical ventilation and acute circulatory failure, ΔVTI 100 accurately predicts fluid responsiveness.

The effect of adrenergic β2 receptor agonist on paraplegia following clamping of abdominal aorta

IntroductionSurgical repair of an aortic aneurysm might be complicated by spinal cord injury and paraplegia. Since β-adrenoreceptor agonists showed neuroprotective effects, the study was designed to investigate the effect of clenbuterol on post-aortic clamping paraplegia and to identify if there is hyperemia associated with paraplegia.Material and methodsMaterial and methods: Thirty rabbits were divided into two groups: 15 control and 15 experimental (given clenbuterol 9 mg in drinking water 24 h prior to surgery). All the animals were subjected to laparotomy whereas the abdominal aorta was identified. Using a vascular clamp, the abdominal aorta was clamped just distal to the renal arteries. Abdominal aortic blood flow was recorded with a transonic flow meter. The neurological assessment was made according to Tarlov’s Neurological Scale upon recovering from anesthesia. Anal sphincter tonus and bladder sphincter function were also checked.ResultsFour rabbits (2 control and 2 experimental) developed complete paraplegia within 30 min of cross-clamping of the aorta. Of the 13 controls, 77% developed paraplegia, and of the 13 experimental rabbits administered clenbuterol 24 h prior to surgery with 22 min of aortic cross-clamping, 38% developed paraplegia The rabbits which did not develop paraplegia had a minimal increase in aortic blood flow, whereas the rabbits which developed paraplegia had a significant increase in aortic blood flow measurements after aortic decamping.ConclusionsPost-aortic clamping paraplegia is associated with hyperemia and clenbuterol has a significant neuroprotective effect, obviously by preventing an increase in aortic blood flow following unclamping.

Changes in aortic blood flow induced by passive leg raising predict fluid responsiveness in critically ill patients

IntroductionEsophageal Doppler provides a continuous and non-invasive estimate of descending aortic blood flow (ABF) and corrected left ventricular ejection time (LVETc). Considering passive leg raising (PLR) as a reversible volume expansion (VE), we compared the relative abilities of PLR-induced ABF variations, LVETc and respiratory pulsed pressure variations (ΔPP) to predict fluid responsiveness.MethodsWe studied 22 critically ill patients in acute circulatory failure in the supine position, during PLR, back to the supine position and after two consecutive VEs of 250 ml of saline. Responders were defined by an increase in ABF induced by 500 ml VE of more than 15%.ResultsTen patients were responders and 12 were non-responders. In responders, the increase in ABF induced by PLR was similar to that induced by a 250 ml VE (16% versus 20%; p = 0.15). A PLR-induced increase in ABF of more than 8% predicted fluid responsiveness with a sensitivity of 90% and a specificity of 83%. Corresponding positive and negative predictive values (PPV and NPV, respectively) were 82% and 91%, respectively. A ΔPP threshold value of 12% predicted fluid responsiveness with a sensitivity of 70% and a specificity of 92%. Corresponding PPV and NPV were 87% and 78%, respectively. A LVETc of 245 ms or less predicted fluid responsiveness with a sensitivity of 70%, and a specificity of 67%. Corresponding PPV and NPV were 60% and 66%, respectively.ConclusionThe PLR-induced increase in ABF and a ΔPP of more than 12% offer similar predictive values in predicting fluid responsiveness. An isolated basal LVETc value is not a reliable criterion for predicting response to fluid loading.

Cardiovascular effects of nociceptin in unanesthetized mice.

We evaluated the systemic hemodynamic effects induced by nociceptin (NC) and NC-related peptides, including the NC receptor antagonist [Phe1psi(CH2-NH)Gly2]NC(1-13)NH2 ([F/G]NC(1-13)NH2) in unanesthetized normotensive Swiss Morini mice. Bolus intravenous injection of NC decreased mean blood pressure and heart rate. The hypotensive response to 10 nmol/kg NC lasted <10 minutes, whereas a more prolonged hypotension was evoked by 100 nmol/kg (from 114+/-3 to 97+/-2 mm Hg at 10 minutes, P<0.01). The latter dose reduced heart rate from 542+/-43 to 479+/-31 beats/min (P<0.05) and increased aortic blood flow by 41+/-5% (P<0.05). Hypotension and bradycardia were also evoked by NC(1-17)NH2 and NC(1-13)NH2 fragments, whereas NC(1-13)OH and NC(1-9)NH2 were ineffective. Thiorphan, an inhibitor of neutral endopeptidase 24.11, enhanced the hypotension induced by NC(1-13)NH2 and revealed the ability of NC(1-13)OH to decrease mean blood pressure. [F/G]NC(1-13)NH2, a recently synthesized antagonist of the NC receptor, did not alter basal mean blood pressure or heart rate, but it prevented the hypotension, bradycardia, and increase in aortic blood flow evoked by NC. In contrast, [F/G]NC(1-13)NH2 did not alter the hypotension induced by bradykinin or endomorphin-1 (a micro-receptor agonist), and the bradycardia induced by leu-enkephalin (a delta-receptor agonist) or U504885 (a synthetic kappa-receptor agonist). In conclusion, NC and some of its fragments cause hypotension and bradycardia and increase aortic blood flow in mice, with the NC(1-13) sequence being critical for these biological effects. Our results also demonstrate that the compound [F/G]NC(1-13)NH2 is a potent and selective antagonist of the NC receptor in vivo.

Comparison of the myocardial effects of desflurane and isoflurane in healthy patients: assessment by continuous oesophageal aortic blood flow echo-Doppler

Experimentally, desflurane causes a moderate positive inotropic effect and a transient increase in arterial pressure with rapid increases in concentration compared with isoflurane. We used a continuous oesophageal aortic blood flow echo Doppler device to study the myocardial effects of equi-anaesthetic concentrations of isoflurane and desflurane in 32 healthy patients undergoing superficial surgery. After induction of anaesthesia with midazolam, etomidate and fentanyl general anaesthesia was maintained in 16 patients with 0.6% end-expired concentration of isoflurane and in 16 patients with 3% end expired concentration of desflurane. Isoflurane induced a rapid decrease in aortic blood flow (ABF) which remained almost stable whereas desflurane induced an early, moderate and transient increase in ABF (1 min after introduction of the halogenated agent, mean ABF was 107 (SD 3)% in the desflurane group vs 95 (9)% in isoflurane group compared with control values before introduction of the inhalation agent; P = 0.005), followed by a marked secondary decrease in ABF. The maximal decrease in ABF reached 71 (15)% of its initial value in the desflurane group compared with 80 (14)% in the isoflurane group (ns). Neither agent caused significant changes in other variables except for PE'CO2 which decreased in both groups. Continuous ABF echo-Doppler monitoring demonstrated an early transient positive inotropic effect of desflurane.

Hypotensive mechanism of [Leu13]motilin in dogs in vivo and in vitro

The effects of [Leu13]motilin were examined in vivo after its intravenous administration into anesthetized dogs and in vitro with isolated preparations of canine mesenteric artery. [Leu13]Motilin (0.1-10 nmol·kg-1, i.v.) induced both strong and clustered phasic contractions in the gastric antrum and duodenum. At doses of over 1 nmol·kg-1, [Leu13]motilin also produced transient decreases in arterial blood pressure, left ventricular pressure, maximum rate of rise of left ventricular pressure, and total peripheral resistance, and an increase in aortic blood flow and heart rate. A selective motilin antagonist, GM-109 (Phe-cyclo[Lys-Tyr(3-tBu)-betaAla]betatrifluoroacetate), completely abolished the gastric antrum and duodenal motor responses induced by [Leu13]motilin. In contrast, hypotension induced by [Leu13]motilin (1 nmol·kg-1) was unchanged in the presence of GM-109. In isolated mesenteric artery preparations precontracted with U-46619 (10-7 M), [Leu13]motilin (10-8-10-5 M) induced an endothelium-dependent relaxation, and this was inhibited by a pretreatment with Nomega-nitro-L-arginine, a competitive inhibitor of NO synthase (10-4 M). A high dose (10-4 M) of GM-109 slightly decreased [Leu13]motilin-induced relaxation, and shifted the concentration-response curve of [Leu13]motilin to the right. However, the pA2 value (4.09) of GM-109 for [Leu13]motilin in the present study was conspicuously lower than that previously demonstrated in the rabbit duodenum (7.37). These results suggest that [Leu13]motilin induces hypotension via the endothelial NO-dependent relaxation mechanism and not through the receptor type that causes upper gastrointestinal contractions.Key words: motilin, gastrointestinal motility, hypotension, hemodynamics, anesthetized dog, mesenteric artery, endothelium, nitric oxide.

Successful transplantation of adult-sized kidneys into infants requires maintenance of high aortic blood flow.

Nationally, results of renal transplantation in infants are inferior to those in older children and adults. Within the infant group, best results are obtained with adult-sized kidneys (ASKs) rather than size-compatible pediatric kidneys. However, transplantation of ASKs into infants has an increased risk of acute tubular necrosis and graft loss from vascular thrombosis and primary nonfunction. The aim of this study was to define and understand the hemodynamic changes induced by ASK transplantation, so that outcomes of transplantation in infants can be improved. Nine hemodynamically stable and optimally hydrated infants were studied under a controlled sedation with cine phase-contrast magnetic resonance at three time periods: before transplantation, 8-12 days after transplantation, and 4-6 months after transplantation. Cross-sectional images of both the infant aorta and the adult transplant renal artery were obtained and blood flow was quantitated. Renal volumes were also obtained, and expected renal artery blood flow based on early posttransplant volume was calculated. In addition, renal artery blood flow was determined in 10 in situ native adult kidneys prior to donor nephrectomy. Supplemental nasogastric or gastrostomy tube feeding was carried out during the blood flow study period to optimize intravascular volume. Mean infant aortic blood flows were 331+/-148 ml/min before transplantation, 761+/-272 ml/ min at 8-12 days after transplantation (P=0.0006 with pretransplant flow), and 665+/-138 ml/min at 4-6 months after transplantation (P=0.0001 with pretransplant flow). Mean transplanted renal artery flows were 385+/-158 ml/min at 8-12 days and 296+/-113 ml/min at 4-6 months after transplantation. Transplanted renal artery flows were less than prenephrectomy in situ donor renal artery blood flow (618+/-130 ml/min; P=0.02 and P=0.0003) and expected normal renal artery blood flow (666+/-87 ml/min; P=0.003 and P=0.001) at both 8-12 days and 4-6 months after transplantation. A 26% reduction in renal volume (P=0.003) occurred between the two postoperative time periods, and this paralleled the decrease in posttransplant renal artery flow. One-year graft and patient survival in the nine infants was 100%. The mean serum creatinine levels at 3, 6, and 12 months were 0.43+/-0.10, 0.48+/-0.15, and 0.49+/-0.16 mg/dl. This study is the first to quantitatively document the blood flow changes occurring after ASK transplantation in infants. There was a greater than two-fold increase in aortic blood flow after ASK transplantation, and this increase was sustained for at least 4 months and appeared to be driven by the blood flow demand of the ASK. However, actual posttransplant renal artery blood flow was significantly less than normal renal artery flow. Our study suggests that aggressive intravascular volume maintenance may be necessary to achieve and maintain optimum aortic blood flow, so as not to further compromise posttransplant renal artery flow and to avoid low-flow states that could induce acute tubular necrosis, vascular thrombosis, or primary nonfunction.

Hypotensive mechanism of [Leu13]motilin in dogs in vivo and in vitro.

The effects of [Leu13]motilin were examined in vivo after its intravenous administration into anesthetized dogs and in vitro with isolated preparations of canine mesenteric artery. [Leu13]Motilin (0.1-10 nmol x kg(-1), i.v.) induced both strong and clustered phasic contractions in the gastric antrum and duodenum. At doses of over 1 nmol x kg(-1), [Leu13]motilin also produced transient decreases in arterial blood pressure, left ventricular pressure, maximum rate of rise of left ventricular pressure, and total peripheral resistance, and an increase in aortic blood flow and heart rate. A selective motilin antagonist, GM-109 (Phe-cyclo[Lys-Tyr(3-tBu)-betaAla] trifluoroacetate), completely abolished the gastric antrum and duodenal motor responses induced by [Leu13]motilin. In contrast, hypotension induced by [Leu13]motilin (1 nmol x kg(-1)) was unchanged in the presence of GM-109. In isolated mesenteric artery preparations precontracted with U-46619 (10(-7) M), [Leu13]motilin (10(-8)-10(-5) M) induced an endothelium-dependent relaxation, and this was inhibited by a pretreatment with N(omega)-nitro-L-arginine, a competitive inhibitor of NO synthase (10(-4) M). A high dose (10(-4) M) of GM-109 slightly decreased [Leu13]motilin-induced relaxation, and shifted the concentration-response curve of [Leu13]motilin to the right. However, the pA2 value (4.09) of GM-109 for [Leu13]motilin in the present study was conspicuously lower than that previously demonstrated in the rabbit duodenum (7.37). These results suggest that [Leu13]motilin induces hypotension via the endothelial NO-dependent relaxation mechanism and not through the receptor type that causes upper gastrointestinal contractions.

Arterial expansive remodeling induced by high flow rates.

The effects of chronic increase in aortic blood flow on arterial wall remodeling were investigated in vivo with the use of an aortocaval fistula (ACF) model in rats. Phasic hemodynamics and aortic wall structure upstream and downstream in 30 male Wistar rats with ACF and 30 sham-operated rats were compared immediately and 2 mo after the ACF was opened in anesthetized rats. Opening the ACF upstream acutely decreased aortic pressure (-30%, P < 0.001) and increased aortic blood velocity (x12, P < 0.001), blood flow (x9, P < 0.001), wall shear stress (x10, P < 0.001) and guanosine 3',5'-cyclic monophosphate (cGMP) wall content (+50%, P < 0.01). After 2 mo, aortic pressure decreased (-22%, P < 0.001) and aortic blood velocity, diameter, and blood flow increased (+114%, P < 0.001; +60%, P < 0.001; and +250%, P < 0.001; respectively) compared with the control group. Aortic wall shear stress and cGMP wall content dropped over time and tended to recover control values; aortic wall tensile stress was higher than in the control group (P < 0.05). Medial cross-sectional area and elastin and collagen contents increased (+38%, P < 0.01; +50%, P < 0.01; and +30%, P < 0.05, respectively) and were associated with smooth muscle cell hypertrophy) (+23%, P < 0.05), despite a decrease in arterial wall thickness (-13%, P < 0.01). Opening the ACF downstream acutely decreased aortic pressure (-30%, P < 0.001) without any change in aortic blood velocity, diameter, blood flow, shear stress, and cGMP wall content. After 2 mo, pressure, blood velocity, shear stress, and cGMP wall content decreased (-22%, P < 0.001; -31%, P < 0.01; -46%, P < 0.02; and -50%, P < 0.05; respectively) and diameter and blood flow were unchanged; smooth muscle cell hypertrophy and hypoplasia were the only observed changes in the aortic wall structure. These results suggest that both shear and tensile stresses are involved in the aortic wall remodeling. Increase in shear stress likely induces expansive remodeling in relation to flow-dependent vasodilation, whereas increase in tensile stress is responsible for medial hypertrophy and fibrosis.

Haemodynamic effects of the calcium facilitator Bay K‐8644 in rats following vascular calcium overload

1. The haemodynamic effects of the Ca2+ facilitator Bay K-8644 (Bay) were studied in a model of calcinosis induced by acute treatment with vitamin D3 and nicotine administration over 4 days with 13 days of recovery. 2. Calcium content of the left ventricular myocardium increased 8-9 fold, while aortic Ca2+ levels increased up to 12-fold in treated animals. There were minimal changes in the ECG and no change in the level of plasma alpha-hydroxy-butyrate-dehydrogenase, a cardiac specific enzyme which increases during ischaemia. Significant increases in pulse pressure (PP) were seen in anaesthetized and conscious calcinotic rats, with no increase in cardiac output index (DABF) or systemic vascular resistance. However, aortic rigidity (AORI) was significantly elevated in the calcinotic group under anaesthesia. 3. In both control and calcinotic rats, pressor responses to i.v. Bay were exclusively mediated by an increase in aortic blood flow (DABF) as lower body vascular resistance (TLBVR) did not change. The increase in DABF at low doses (0.1-1 microgram kg-1) of Bay probably resulted from an increase in venous return induced by the agonist, as Bay had little effect on cardiac contractility over this dose range (as estimated by left ventricular dp/dtmax) and did not cause tachycardia. At higher doses (10-1000 micrograms kg-1), Bay significantly increased LV dp/dt. Bay caused dose-related increases in AORI in pithed calcinotic rats, but a decrease in AORI in control animals. 4. The calcinosis model, which incorporates a recovery period to obviate the acute effects of nicotine and/or vitamin D3 treatment, results in long-term tissue calcium accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Decreased poststenotic flow disturbance during drag reduction by polyacrylamide infusion without increased aortic blood flow

The infusion of polyacrylamide in open chest rats has been reported to increase aortic blood flow and the effect has been ascribed to the “drag reduction” properties of these compounds. In six anesthetized dogs the infusion of polyacrylamide to a total dose of 2 mg/kg caused a reduction in midline and separation zone Doppler spectral broadening in the common carotid artery poststenotic velocity field. This apparent reduction in poststenotic turbulence was interpreted as indicating the presence of a drag reducing effect. Despite this demonstration that polyacrylamide was present in the blood in drag reducing concentrations no increase in aortic blood flow was produced.

Cardiovascular effect of a novel substance, 3-[2-[4-(o-methoxyphenyl)-1-piperazinyl] ethyl]-2,4 (1H, 3H)-quinazolinedione monohydrochloride (SGB 1534)

During the search for a new antihypertensive substance, the author and his co-workers found that SGB 1534 has a potent vasodepressor action. However, its pharmacological properties are not well-known. Therefore, we examined the cardiovascular effect and the site of action of this substance. In anesthetized beagle dogs, SGB 1534 (0.01 micrograms/kg, i.v.) caused a 8% fall in mean systemic blood pressure. It caused a transient increase in aortic blood flow. Heart rate was increased transiently and was decreased thereafter. Systemic vascular resistance was reduced, but Vpm and time constant "T" were little influenced by this substance. The phenylephrine-induced vasopressor effect was eliminated by SGB 1534. In dogs pretreated with propranolol and prazosin, the norepinephrine-induced vasopressor effect was suppressed by yohimbine, but not by SGB 1534. In dogs pretreated with prazosin and yohimbine, isoproterenol-induced increase in heart rate was not influenced by this substance. The results indicate that SGB 1534 is a potent alpha 1-adrenoreceptor blocking substance.

Cardiovascular responses to alpha-melanocyte stimulating hormone during the perinatal period in sheep.

To determine the effects of alpha-melanocyte stimulating hormone (alpha MSH) on the circulation of undisturbed fetal sheep and young lambs and to explore possible mechanisms of actions, we examined the responses of ascending aortic blood flow, heart rate, stroke volume, and arterial blood pressure to a single intravenous injection of alpha MSH, ACTH, cortisol and to alpha MSH after beta-adrenergic blockade. We also measured cardiac output and organ blood flows before and after alpha MSH injection by the radionuclide labeled microsphere technique. alpha MSH increased ascending aortic blood flow from 249 +/- 23 to 327 +/- 30 ml X min-1 X kg-1 (P less than 0.001), heart rate from 111 +/- 10 to 126 +/- 11 min-1, (P less than 0.001) and stroke volume from 2.32 +/- 0.21 to 2.75 +/- 0.20 ml X kg-1, (P less than 0.001) in 10 young lambs 15-30-day-old. alpha MSH decreased mean systemic arterial blood pressure from 42.6 +/- 1.7 to 39.3 +/- 1.6 mmHg (P less than 0.001) in fetal sheep and min-1, (P less than 0.001) and stroke volume from 2.32 +/- 0.21 to 2.75 +/- 0.20 ml X kg-1, (P less than 0.001) in 10 young lambs 15-30-days-old. alpha MSH decreased mean systemic arterial blood pressure from 42.6 +/- 1.7 to 39.3 +/- 1.6 mmHg (P less than 0.001) in fetal sheep and from 77.5 +/- 4.5 to 72.7 +/- 4.3 mmHg (P less than 0.001) in young lambs. In six additional young lambs (20-35-day-old) cardiac output, measured by microspheres, increased with alpha MSH from 216 +/- 20 to 261 +/- 19 ml X min-1 X kg-1 (P less than 0.001). alpha MSH also increased blood flow to the myocardium from 104 +/- 22 to 151 +/- 26 ml X min-1 X 100 g-1 (P less than 0.001), to the adrenals from 195 +/- 38 to 243 +/- 41 ml X min-1 X 100 g-1, (P less than 0.05), and to the lungs from 157 +/- 31 to 468 +/- 81 ml X min-1 X 100 g-1 (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

85 CARDIOVASCULAR RESPONSES TO ALPHA MSH IN THE FETAL AND NEWBORN SHEEP

The cardiovascular effects of alphaMSH and related peptides have not been studied extensively. Although there are some observations of adult animals, no studies have been conducted of the fetal and neonatal circulation. Therefore we examined the responses to an i.v. bolus of 75 micrograms of alphaMSH on heart rate (HR) mean arterial pressure (MAP), aortic blood flow (ABF), and stroke volume (SV) in 9 newborn lambs (15 to 27 days) and in fetal sheep (110 to 133 days gestation). An increase in ABF and decrease in MAP was observed following alphaMSH injection in the fetus (140 ± 38 to 158 ± 40 ml/Kg/min, p 0.005 and 41.7 ± 1.8 to 39.0 ± 1.6 mm Hg p 0.0125 respectively) (mean ± SE). There was no significant modification of fetal HR or SV. In the newborn, there was an increase in ABF (257 ± 25 to 326 ± 33 ml/Kg/min, p 0.005) and HR (106 ± 8 to 122 ± 10 beats/min, p 0.005) and a decrease in MAP (73 ± 4 to 69 ± 5, p 0.005) after alphaMSH injection. There was no modification of the SV in the newborn lamb. Beta blockade with propranolol (lmg/Kg) did not prevent the rise in ABF and HR observed after the same dose of alphaMSH in the newborn lamb. These results indicate that alphaMSH is able to increase the left ventricular output in the newborn and fetal sheep and its mechanism of action is not through beta adrenergic receptor (Supported by NIH Grant HLO6285 and HD06619).

Direct cardiac action of E. coli endotoxin.

SummaryE. coli endotoxin exerts a direct vasoconstrictor effect on the coronary vessels. E. coli endotoxin also causes an initial increase in aortic blood flow, myocardial contractile force, and left ventricular work done. These initial cardiac responses can be attenuated by depleting catecholamines or by blocking beta-adrenergic receptor sites. The initial responses are somewhat modified by depletion of histamine indicating that catecholamines are not the sole mediators for the initial effects of endotoxin.The author gratefully acknowledges the advice of Professor Shoji Saito (Nihon University School of Medicine, Department of Pharmacology, Tokyo, Japan) and the technical assistance of Mr. M. H. Hayman and Miss L. A. Anderson (both senior Medical Students at LSU Medical School in New Orleans). This study was partially supported by the Institutional Research Grant from Louisiana State University School of Medicine in New Orleans (No. 456-99-8602).

The effect of aorto-iliac occlusion and sympathectomy on aorto-iliac blood flow: An experimental study

A study of aorto-iliac blood flow was performed before and after sympathectomy in the dog anesthetized with sodium pentobarbital. Sodium pentobarbital was found to increase aortic blood flow as much as sympathectomy. Blood flow to one extremity was increased when the other was occluded and this increase remained even after flow was re-established. Sympathectomy performed on the occluded side resulted in no decrease in flow after release; however, if performed on the opposite side, the flow on the occluded side after release was markedly reduced. Two hours of aortic occlusion produced a 30 to 50 per cent reduction in aortic blood flow from the preocclusion level. Sympathectomy caused more than a twofold increase in aortic blood flow after aortic occlusion, but no appreciable increase was noted before occlusion. Sympathectomy protects against decreased blood flow after temporary vascular occlusion.