Superior Mesenteric Artery Vascular Resistance Research Articles

INTESTINAL HEMODYNAMIC EFFECTS OF MILRINONE IN ASPHYXIATED NEWBORN PIGS AFTER REOXYGENATION WITH 100% OXYGEN

Neonatal asphyxia can result in poor perfusion, vasoconstriction, and decreased oxygen delivery in the intestine. Milrinone increases myocardial contractility and causes peripheral vasodilatation. We examined the dose-response of milrinone on the intestinal circulation, oxygen metabolism, and injury in a newborn piglet model of asphyxia-reoxygenation. Piglets (aged 1-3 days, weighing 1.5-2.3 kg) were acutely instrumented to measure superior mesenteric artery (SMA) flow and oxygen delivery. After stabilization, hypoxia (inspired oxygen concentration, 0.08-0.15) was induced for 2 h followed by reoxygenation with 100% O2 for 1 h then 21% O2 for 3 h. At 2 h of reoxygenation, saline or milrinone infusion at doses of 0.25, 0.5, or 0.75 microg/kg per min was given for 2 h in a blinded randomized fashion (n = 7 per group). Hemodynamic and oxygen transport parameters were analyzed at predefined time points. Intestinal tissue lactate concentrations, plasma milrinone levels, and intestinal glutathione redox status were determined at the end of the experiment. In the intestinal tract, milrinone significantly increased SMA flow and oxygen delivery while decreasing vascular resistance at a dose of 0.75 microg/kg per min (P < 0.05, ANOVA). A modest increase in SMA flow and oxygen delivery was found with milrinone at 0.5 microg/kg per min. Plasma milrinone levels correlated with SMA flow and vascular resistance (r = 0.5 and r = -0.6, respectively, P < 0.05). Intestinal lactate concentrations and histopathology were not significantly different among groups. Oxidized glutathione correlated with SMA vascular resistance and negatively with milrinone levels (r = 0.6 and r = -0.5, P < 0.05). When used to treat shock in a newborn model of asphyxia-reoxygenation, milrinone dose-dependently increases SMA flow and oxygen delivery with a significantly decreased SMA vascular resistance at higher doses.

Mesenteric vasoconstriction triggers nitric oxide overproduction in the superior mesenteric artery of portal hypertensive rats

Background & Aims: Vasoconstriction of the superior mesenteric artery (SMA) is the earliest hemodynamic event occurring after partial portal vein ligation (PVL). We tested the hypothesis that this early vasoconstriction of the SMA may initiate eNOS up-regulation in PVL. Methods: Portal hypertension with or without mesenteric vasoconstriction was induced by differentially calibrated stenosis of the portal vein (PVL-20G and PVL-18G, respectively). In a separate group of rats, mesenteric vasoconstriction was achieved by renal artery ligation. Sham-operated rats were used as controls. Effects of vasoconstriction of the SMA in PVL and RAL rats were evaluated by measuring perfusion pressure changes in isolated SMA beds in response to methoxamine, nitric oxide synthase activity, and eNOS protein expression. Mean arterial pressure, portal pressure, and SMA blood flow were measured by catheterization and Doppler flowmetry. SMA vascular resistance was calculated from arterial pressure, portal pressure, and SMA flow. Results: There was a significant increase in SMA vascular resistance in PVL-20G (2.33 ± 0.13 vs. 1.22 ± 0.03 mm Hg/% flow; P < 0.05) and RAL (2.32 ± 0.18 vs. 1.18 ± 0.02 mm Hg/% flow; P < 0.05) but not in PVL-18G, showing mesenteric vasoconstriction in both PVL-20G and RAL groups. The mesenteric vasculature of PVL-20G and RAL animals showed hyporeactivity to methoxamine ( P < 0.01). Whereas both PVL groups were portal hypertensive ( P < 0.01), RAL rats were not. The SMA hyporeactivity of PVL-20G and RAL rats was corrected by N G -monomethyl- l-arginine, and nitric oxide synthase enzyme activity was significantly higher in PVL-20G and RAL rats ( P < 0.05). Conclusions: Mesenteric arterial vasoconstriction plays a triggering role in up-regulation of eNOS catalytic activity in the SMA of portal hypertensive rats.

Effect of the type IV phosphodiesterase inhibitor Ro 20-1724 on catecholamine-induced alterations in regional vascular resistance and regional blood flow.

Type IV phosphodiesterase inhibitors have been studied in multiple disease processes that commonly afflict patients who are treated with catecholamine infusions. To examine whether type IV phosphodiesterases alter catecholamine-induced changes in systemic and regional hemodynamic parameters, we examined the effects of Ro 20-1724 on rats during dobutamine, epinephrine, isoproterenol, and norepinephrine infusions. Twenty-six Sprague-Dawley rats received either Ro 20-1724 or vehicle. After central and regional hemodynamic monitoring was initiated, animals received increasing doses of two of the four catecholamines. In the absence of catecholamines, Ro 20-1724 infusion caused a significant increase in heart rate and a trend toward an increase in superior mesenteric artery blood flow. Ro 20-1724 attenuated the increase in blood pressure caused by epinephrine but had no effect on the dobutamine-, isoproterenol-, or norepinephrine-induced changes in blood pressure. Ro 20-1724 had no effect on catecholamine-induced changes in renal, carotid, and hindquarter vascular resistance but did attenuate the decrease in superior mesenteric artery vascular resistance caused by isoproterenol. Type IV phosphodiesterase inhibition in combination with catecholamines has no adverse effects on regional hemodynamics; however, it can inhibit the ability of epinephrine infusion to increase blood pressure.

Effects of a Continuous Epinephrine Infusion on Regional Blood Flow in Awake Newborn Piglets

Objective: To determine the effects of a continuous epinephrine infusion on renal and mesenteric blood flow in both healthy newborn piglets and animals subjected to hemorrhagic shock. Methods: Superior mesenteric artery (SMA) and left renal artery ultrasonic flow probes were implanted into 16 1- to 3-day-old piglets. Two days later, the effects of epinephrine on SMA and renal blood flow, mean arterial pressure (MAP) and central venous pressure were measured in conscious, non-sedated normovolemic piglets. Epinephrine doses of 0.2, 0.4, 0.8, 1.6 and 3.2 µg/kg·min were used in random order. Piglets were subsequently hemorrhaged (20 ml/kg) to mild hypotension and again received epinephrine infusion in the same doses. Results: Doses of epinephrine less than 3.2 µg/kg·min had no significant effects on renal or mesenteric arterial flow. At 3.2 µg/kg·min of epinephrine during normovolemia, there was a significant decrease in SMA blood flow (34% [SD 42], p < 0.05) and increase in SMA vascular resistance (147% [SD 114], p < 0.05). Similar results were shown during hypovolemia, SMA flow decreased by 32% (SD 33), and SMA vascular resistance increased by 220.3% (SD 177). At 3.2 µg/kg·min renal artery flow decreased by 43% (SD 21) during normovolemia and a similar decrease occurred during hypovolemia, 37% (SD 31). Renal vascular resistance increased by about 200% at this dose (normovolemia 211% [SD 185], hypovolemia 186% [SD 150], p < 0.01). Low-to-moderate dose epinephrine caused no significant change in SMA or renal blood flow. During hypovolemia low dose epinephrine infusion was associated with a trend to increased SMA blood flow. Conclusion: Low-dose epinephrine does not cause vasoconstriction in the renal or mesenteric circulations during normovolemia or hypovolemia. High doses of epinephrine above 1.6 µg/kg·min may cause renal or mesenteric ischemia, in either the normovolemic or hypovolemic neonate.

Hypotensive and regional haemodynamic effects of exercise, fasted and after food, in human sympathetic denervation.

1. In human sympathetic denervation due to primary autonomic failure, food and exercise in combination may produce a cumulative blood pressure lowering effect due to simultaneous splanchnic and skeletal muscle dilatation unopposed by corrective cardiovascular reflexes. We studied 12 patients with autonomic failure during and after 9 min of supine exercise, when fasted and after a liquid meal. Standing blood pressure was also measured before and after exercise. 2. When fasted, blood pressure fell during exercise from 162 +/- 7/92 +/- 4 to 129 +/- 9/70 +/- 5 mmHg (mean arterial pressure by 22 +/- 5%), P < 0.0005. After the meal, blood pressure fell from 159 +/- 8/88 +/- 6 to 129 +/- 6/70 +/- 4 mmHg (mean arterial pressure by 22 +/- 3%), P < 0.0001, and further during exercise to 123 +/- 6/61 +/- 3 mmHg (mean arterial pressure by 9 +/- 3%), P < 0.01. The stroke distance-heart rate product, an index of cardiac output, did not change after the meal. During exercise, changes in the stroke distance-heart rate product were greater when fasted. 3. Resting forearm and calf vascular resistance were higher when fasted. Calf vascular resistance fell further after exercise when fasted. Resting superior mesenteric artery vascular resistance was lower when fed; 0.19 +/- 0.02 compared with 0.32 +/- 0.06, P < 0.05. After exercise, superior mesenteric artery vascular resistance had risen by 82%, to 0.53 +/- 0.12, P < 0.05 (fasted) and by 47%, to 0.29 +/- 0.05, P < 0.05 (fed). 4. On standing, absolute levels of blood pressure were higher when fasted [83 +/- 7/52 +/- 7 compared with 71 +/- 2/41 +/- 3 (fed), each P < 0.05]. Subjects were more symptomatic on standing post-exercise when fed. 5. In human sympathetic denervation, exercise in the fed state lowered blood pressure further than when fasted and worsened symptoms of postural hypotension.

Abnormal regional blood flow responses during and after exercise in human sympathetic denervation.

1. Blood pressure, superior mesenteric artery (SMA) and skeletal muscle blood flow, cardiac index (CI) and systemic vascular resistance responses to supine leg exercise were measured in six age-matched normal subjects (controls) and in eleven subjects with sympathetic denervation due to primary autonomic failure (AF). 2. During exercise, blood pressure rose in controls but fell markedly in AF. After exercise, blood pressure rapidly returned to baseline in controls but remained low in AF. During exercise, systemic vascular resistance fell in controls and AF but tended to fall further in AF and remained low post exercise. CI increased similarly in controls and AF. 3. During exercise, SMA blood flow fell similarly in controls and AF, but the fall initially was slower in AF; recovery was more rapid post exercise in controls. SMA vascular resistance tended to rise less and more slowly in AF and remained elevated post exercise. 4. Forearm muscle (FM) blood flow and FM vascular resistance did not change from resting values in controls or AF post exercise. After exercise, leg muscle (LM) blood flow rose and LM vascular resistance fell equally in both groups although LM blood flow remained elevated, 10 min post exercise in AF. 5. In sympathetically denervated humans, increased blood flow (due to excessive vasodilatation, lack of sympathetic restraint, or both) in leg muscle during and after exercise in combination with impaired splanchnic vasoconstriction in the early stages of exercise may have contributed to exercise-induced hypotension.

Central defects of autonomic function in secondary progressive multiple sclerosis: observations based on cardiovascular and growth hormone responses to clonidine

The haemodynamic, autonomic and hormonal effects of the centrally acting sympatholytic drug clonidine have been studied in 10 patients with secondary progressive multiple sclerosis (MS) and 10 age- and sex-matched normal subjects (controls). Detailed physiological studies, previously described in these 10 MS patients, indicated that none had postural hypotension or an abnormal Valsalva manoeuvre; six, however, had impaired responses to a range of pressor tests, suggestive of a central autonomic abnormality. In the controls after clonidine, there was a fall in blood pressure and superior mesenteric artery vascular resistance. Finger temperature and growth hormone levels rose. In the MS patients after clonidine, the haemodynamic responses varied. In five out of ten MS patients, as in the controls, there was a fall in blood pressure and superior mesenteric vascular resistance, while finger temperature rose. There was no haemodynamic response to clonidine in the other five MS patients. In eight out of ten MS patients there was no rise in plasma growth hormone levels after clonidine. The abnormal haemodynamic responses to clonidine, taken in conjunction with the previous physiological studies, suggest involvement of central sympathetic interconnections in five of the MS patients, probably as part of the demyelinating process. The impaired growth hormone response to clonidine occurred in a greater number of patients and may indicate lesions in the hypothalamus. These observations in MS patients, without overt clinical evidence of autonomic failure, indicate that the haemodynamic and growth hormone responses to clonidine may be an early indicator of autonomic dysfunction involving central autonomic centres and pathways.

The effect of captopril on the superior mesenteric artery and portal venous blood flow in normal man.

1. Measurements of superior mesenteric artery and portal venous blood flow were made non-invasively along with systemic and other regional (cardiac index, forearm and cutaneous blood flow) vascular responses to acute ingestion of the ACE inhibitor captopril (50 mg) or placebo (50 mg vitamin C), in 12 healthy subjects while supine and during head-up tilt. 2. After captopril, superior mesenteric artery and portal blood flow rose markedly with a reduction in superior mesenteric artery vascular resistance. Supine blood pressure was unchanged but cardiac index and forearm blood flow rose; during head-up tilt, blood pressure fell in some subjects. 3. There was a rise in levels of plasma renin activity and a fall in levels of plasma angiotensin II after captopril. After placebo, there were no significant changes in splanchnic blood flow, systemic or other regional responses and in biochemical measurements, while supine. 4. Our studies indicate that captopril is a potent dilator of the splanchnic vascular bed and suggest that this action may contribute to its therapeutic effects. The studies indicate a role for angiotensin II in the control of this large vascular bed although other agents (bradykinin, prostacyclin) may contribute.

Superior mesenteric artery vascular resistance is higher in hypertensives and is lowered by clonidine

Superior mesenteric artery vascular resistance is higher in hypertensives and is lowered by clonidine

Superior mesenteric artery vascular resistance is higher in hypertensives and is lowered by clonidine

Cardiovascular Medicine Unit, Department of Medicine, St Mary's Hospital Medical School/Imperial College and the Autonomic Unit, Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.

Comparative hemodynamic effects of selective superior mesenteric arterial and peripheral intravenous glucagon infusions

This experiment was designed to determine whether any hemodynamic benefits attend administration of equal pharmacologic doses of glucagon (1 μg/kg/m) by continuous intravenous infusion (Group I, n = 6) versus selective intraarterial infusion (Group II, n = 6) via the superior mesenteric artery (SMA) in dogs. Cardiac output, heart rate, mean arterial pressure, total peripheral resistance, pulmonary vascular resistance, superior mesenteric artery flow (SMAQ), SMA vascular resistance, and portal venous pressure were measured at baseline (BL) and at 5, 15, 30, and 45 min during glucagon infusion. SMAQ virtually doubled at 5 min from a baseline of 570 ± 60 ml/min to 1158 ± 146 ml/min in Group I ( P < 0.001), and from a baseline of 527 ± 171 to 1018 ± 331 ml/min in Group II ( P < 0.002). SMAQ was significantly higher in Group I at 30 and 45 min compared to Group II ( P < 0.03) despite similar peripheral plasma glucagon levels. SMA vascular resistance was significantly lowered in both groups, with a greater reduction occurring during intravenous glucagon administration at 45 min ( P < 0.05). Changes in systemic hemodynamic parameters, as well as glucagon and glucose levels were not statistically different between Groups I and II at any time period. Glucagon is a potent mesenteric vasodilator and the resultant profound splanchnic hemodynamic effects are as marked during intravenous administration as during selective SMA infusion.

Glucagon and canine mesenteric hemodynamics: Effects on superior mesenteric arteriovenous and nutrient capillary blood flow

The objective of this investigation was to define the splanchnic hemodynamic effects of parenterally administered glucagon in a canine model. Measurements in six dogs at baseline and at 10, 20, and 30 min during constant intravenous infusion of glucagon at 1 μg/kg/min included: Cardiac output (CO), mean arterial pressure, total peripheral vascular resistance (TPR), superior mesenteric artery flow (SMAQ), portal venous pressure (PVP), superior mesenteric artery vascular resistance (SMAR), percentage SMA flow through arteriovenous anastomoses (AVA%) determined by 99mTc microsphere technique, as well as volume flow through AVA (AVAQ), and volume flow through the SMA nutrient capillary circulation (NCQ). SMAQ rose significantly and disproportionately compared to the rise in CO. SMAQ more than doubled from a mean of 448 ± 124 cc at baseline to a mean of 921 ± 321 cc at 10 min, and remained elevated throughout drug infusion. SMAR and TPR both decreased significantly. Although percentage shunt was low at baseline, 1.79 ± 0.94%, and did not change, both AVAQ and NCQ increased significantly during drug infusion. The increase in AVAQ was transient, but NCQ remained elevated throughout infusion. PVP increased significantly, and the change in PVP correlated significantly with the change in AVAQ at 30 min, a time when AVAQ was not elevated significantly above baseline levels. Nutrient capillary flow comprised ≥98% of total SMAQ during the experiment and, along with total SMAQ, doubled and remained elevated throughout drug infusion. Although glucagon may increase PVP by slightly increasing the absolute volume of mesenteric shunt flow, its primary action is that of a potent mesenteric arterial dilator, increasing NCQ strikingly more than AVAQ.

Responses to exogenous dibutyryl adenosine 3',5'-monophospate of cardiac output and blood flow in the renal, superior mesenteric and carotid arteries in anesthetized dogs.

Changes in the cardiac output and blood flow in the renal, superior mesenteric and carotid arteries in anesthetized dogs were observed, using the non-cannulating electromagnetic flow meter. Dibutyryl cyclic-AMP, 5 mg/kg body weight, was given intravenously and the following results were obtained: 1) Dibutyryl cyclic-AMP increased the stroke volume and the cardiac output, and slightly increased the heart rate. These effects appeared 3 to 5 min after administration of dibutyryl cyclic-AMP. 2) The mean systemic blood pressure as well as the central venous pressure fell slightly. 3) The renal and the superior mesenteric artery blood flow increased markedly, but the carotid artery blood flow did not change. 4) Distribution of the cardiac output to the renal and superior mesenteric arteries did not change but distribution to the carotid artery decreased. 5) Total peripheral resistance, renal artery vascular resistance and superior mesenteric artery vascular resistance decreased, and carotid artery vascular resistance decreased slightly. 6) The cardiac output and blood flow were enhanced by aminophylline (3 mg/kg), and were not blocked by propranolol (0.3 mg/kg).

Responses to exogenous adenosine 3',5'-monophosphate of cardiac output and blood flow in the renal, superior mesenteric and carotid arteries in anesthetized dogs.

Changes in the cardiac output and blood flow in the renal, superior mesenteric and carotid arteries in anesthetized dogs were observed, using the non-cannulating electromagnetic flow meter. Dibutyryl cyclic-AMP, 5 mg/kg body weight, was given intravenously and the following results were obtained: 1) Dibutyryl cyclic-AMP increased the stroke volume and the cardiac output, and slightly increased the heart rate. These effects appeared 3 to 5 min after administration of dibutyryl cyclic-AMP. 2) The mean systemic blood pressure as well as the central venous pressure fell slightly. 3) The renal and the superior mesenteric artery blood flow increased markedly, but the carotid artery blood flow did not change. 4) Distribution of the cardiac output to the renal and superior mesenteric arteries did not change but distribution to the carotid artery decreased. 5) Total peripheral resistance, renal artery vascular resistance and superior mesenteric artery vascular resistance decreased, and carotid artery vascular resistance decreased slightly. 6) The cardiac output and blood flow were enhanced by aminophylline (3 mg/kg), and were not blocked by propranolol (0.3 mg/kg).