Rise In Mean Arterial Pressure Research Articles

Acute Blood Pressure Effects and Chronic Hypotensive Action of Calcimimetics in Uremic Rats

A previous study in subtotally nephrectomized (SNX) rats suggested beneficial effects of the calcimimetic R-568 beyond the control of mineral metabolism. This study analyzed potential blood pressure (BP)-lowering effects of R-568. Male Sprague-Dawley rats received two-stage subtotal nephrectomy or sham operation. Telemetry devices were inserted into the abdominal aorta, and BP was measured every 5 min. R-568 (20 mg/kg per d) or solvent was infused for 4 wk followed by once-daily subcutaneous injections for 2 wk. Total body sodium was measured by neutron activation analysis. The uremia-induced increase of mean arterial pressure from baseline to day 42 in SNX solvent rats (103+/-5 to 128+/-14 mmHg, P=0.006) was attenuated by R-568 (104+/-5 to 111+/-8 mmHg; P<0.0001 for difference of slopes). The circadian rhythm was abrogated in SNX rats and not restored by R-568. In sham-operated rats, R-568 had only a minor transient antihypertensive effect. R-568 injection induced a transient rise of mean arterial pressure by 23+/-4 and 26+/-10 mmHg in sham and SNX rats but only by 9+/-3 and 10+/-5 mmHg in solvent-treated rats (P<0.01 versus baseline and solvent versus R-568). Plasma angiotensin-converting enzyme activity and aldosterone levels were similar; food intake and physical activity did not differ throughout the study. In healthy rats, total body sodium was higher after 14 d of R-568 compared with solvent infusion (37.1+/-4 versus 32.5+/-1.4 mmol/kg; P=0.01). The calcimimetic R-568 causes an initial BP increase in sham-operated and uremic rats, which in uremic rats is followed by a marked and sustained antihypertensive effect.

Carotid endarterectomy impairs blood pressure homeostasis by reducing the physiologic baroreflex reserve

To assess the impact of carotid endarterectomy on blood pressure homeostasis and baroreflex function, with particular reference to the presence or absence of significant contralateral carotid artery disease, we conducted a prospective study in 80 patients with symptomatic extracranial carotid disease undergoing carotid endarterectomy in a regional teaching hospital over 2 years. Patients were divided into two groups: the control group (n = 37) had no significant contralateral carotid disease; patients in the diseased group (n = 23) had either >70% stenosis or occlusion of the contralateral carotid artery. Seventeen patients with abnormal heart rhythms, poor quality recordings, or with intermediate degrees of contralateral carotid stenosis were excluded. Three patients who had previously undergone contralateral carotid endarterectomy were separately evaluated. Atheromatous plaque was removed from carotid lumen and the baroreflex mechanism received direct intraoperative stimulation before and after carotid endarterectomy. The main outcome measures were (1) the hemodynamic response to the carotid endarterectomy, baroreflex sensitivity, and operating set point (the resting blood pressure, which the baroreflex mechanism maintains) before and after removal of the atheromatous plaque, and (2) the responsiveness of the ipsilateral baroreceptor mechanism to direct stimulation. The impact of the presence of contralateral carotid stenosis on these variables was also evaluated. Patients in the two groups were comparable for preoperative demographic, medication, and hemodynamic variables. Carotid endarterectomy led to a rise in mean arterial pressure from 81.3 +/- 3.9 mm Hg to 103.5 +/- 4.6 mm Hg ( P < .00001) and from 87.6 +/- 4.3 mm Hg to 94.0 +/- 4.5 mm Hg ( P < .003) in the diseased and control groups, respectively. The magnitude of blood pressure response was significantly greater in the diseased group than in the control group ( P < .00001). This hypertensive shift was not accompanied by the expected fall in heart rate. Direct baroreflex stimulation prior to carotid endarterectomy caused a significantly greater response in the diseased group, suggesting sensitization of the ipsilateral carotid baroreceptor in the presence of contralateral carotid disease. Furthermore, the baroreflex response was obliterated after endarterectomy. There were significant reductions in baroreflex sensitivity and a hypertensive shift in the operating set point, the magnitude of which was significantly greater in patients with contralateral carotid disease. Carotid endarterectomy impairs blood pressure homeostasis through surgical destruction of the ipsilateral carotid baroreflex mechanism. Patients with contralateral carotid stenosis have a reduced baroreflex reserve and show greater baroreflex dysfunction and hemodynamic instability after endarterectomy. These patients are at greater risk of postendarterectomy complications and should be monitored closely.

Negative impact of systemic catecholamine administration on hepatic blood perfusion after porcine liver transplantation

Catecholamines are often administered during and after liver transplantation (LTx) to support systemic perfusion and to increase organ oxygen supply. Some vasoactive agents can compromise visceral organ perfusion. We followed the hypothesis that the vasculature of transplanted livers presents with a higher sensitivity, which leads to an increased vulnerability for flow derangement after application of epinephrine (Epi) or norepinephrine (NorEpi). Hepatic macroperfusion and microperfusion during systemic Epi or NorEpi infusion were measured by Doppler flow and thermodiffusion probes in porcine native, denervated, and transplanted livers (n = 16 in each group). Epi or NorEpi were infused (n = 8 in each subgroup) in predefined dosages (low dose = 5 microg/kg/minute and high dose = 10 microg/kg/minute) over 240 minutes. Systemic cardiocirculatory parameters were monitored continuously. Hepatic perfusion data were compared between all groups at comparable time points and dosages. In all native, denervated, and transplanted liver groups, Epi and NorEpi induced an inconsistent rise of mean arterial pressure and heart rate shortly after onset of infusion in both dosages compared with baseline. No significant differences of cardiovascular parameters at comparable time points were observed. In native livers, Epi and NorEpi induced only temporary alterations of hepatic macrocirculation and microcirculation, which returned to baseline 2 hours after onset of infusion. No significant alterations of hepatic blood flow were detected after isolated surgical denervation of the liver. By contrast, transplanted livers showed a progressive decline of hepatic macrocirculation (33-75% reduction) and microcirculation (39-58% reduction) during catecholamine infusions in a dose-dependent fashion. Characteristics of liver blood flow impairment were comparable for both vasoactive agents. In conclusion, pronounced disturbances of hepatic macrocirculation and microcirculation were observed during systemic Epi and NorEpi infusion after LTx compared with native and denervated livers. Microcirculation disturbances after LTx might be explained by impairment of hepatic blood flow regulation caused by an increased sensitivity of hepatic vasculature after ischemia-reperfusion and by lengthening of vasopressor effects caused by reduced hepatocyte metabolism. Clinicians should be aware of this potentially hazardous effect. Therefore, application of catecholamines after clinical LTx should be indicated carefully.

Lesions of the anteroventral third ventricle region (AV3V) disrupt cardiovascular responses to an elevation in core temperature

Blood flow is redistributed from the viscera to the periphery during periods of heat stress to maximize heat loss. The heat-induced redistribution of blood flow is strongly influenced by nonthermal inputs such as hydration status. At present, little is known about where thermal and nonthermal information is integrated to generate an appropriate effector response. Recently, the periventricular tissue that surrounds the anteroventral third ventricle (AV3V) has been implicated in the integration of thermal and osmotic information. The purpose of the present study was to determine the effects of electrolytic lesions of the AV3V on the cardiovascular response to a passive heat stress in unanesthetized, free-moving male Sprague-Dawley rats. Core temperature was elevated at a constant rate of approximately 0.03 degrees C/min in sham- and AV3V-lesion rats using an infrared heat lamp. Changes in mesenteric and hindquarter vascular resistance were determined using Doppler flow probes, and heat-induced salivation was estimated using the spit-print technique. The rise in mean arterial pressure (MAP), heart rate (HR), and mesenteric resistance in response to elevations in core temperature were all attenuated in AV3V-lesion rats; however, hindquarter resistance was unaffected. Heat-induced salivation was also diminished. In addition, AV3V-lesion rats were more affected by the novelty of the experimental environment, resulting in a higher basal core temperature, HR, and MAP. These results indicate that AV3V lesions disrupt the cardiovascular and salivatory response to a passive heat stress in rats and produce an exaggerated stress-induced fever triggered by a novel environment.

Effect of Methylene Blue on Middle Cerebral Artery Flow Velocity in a Patient With Severe Sepsis Following Clipping of a Cerebral Aneurysm

The use of methylene blue, an inhibitor of guanylate cyclase, has been described in patients with septic shock who are unresponsive to inotropic agents. However, the effects of methylene blue on the human cerebral circulation are not known. This article presents a case report of a 58-year old-female with a clinical presentation compatible with severe sepsis and increasing inotropic requirements following clipping of a cerebral aneurysm. Administration of methylene blue (2 milligrams/kilograms) intravenously was undertaken with monitoring of mean arterial pressure and middle cerebral artery flow velocity (FVm). The effect of methylene blue on mean arterial pressure occurred quite rapidly after initiation of the infusion, allowing downward titration of norepinephrine. Initially, FVm increased in association with an increase in mean arterial pressure, reaching its highest value halfway through the infusion. Subsequently, FVm decreased to baseline by the end of the monitoring period. The rise in mean arterial pressure and increase in FVm were accompanied by a reductionin cerebral vascular resistance assuming intracranial pressure, and the diameter of the insonated vessel was unchanged during and immediately after infusion of methylene blue. Methylene blue did not appear to have a major untoward effect on cerebrovascular resistance in this patient. The limited characterization of cerebrovascular effects provided by this article mandates the need for careful monitoring of cerebrovascular behavior and adequacy during use of methylene blue.

Myogenic Response Reduction by High Blood Glucose Levels in Human Retinal Arterioles

The effect of elevated blood glucose level on the myogenic response of human retinal arterioles to acute increases in blood pressure is investigated. The vascular response to raised blood pressure (Bayliss effect) was measured in 12 healthy volunteers by use of the retinal vessel analyzer (RVA). For a 9-minute period an on-line measurement of the diameter of a retinal branch arteriole was performed. After the first 3 minutes (baseline measurement) a second phase with 3 minutes of isometric exercise caused an acute rise in blood pressure, followed by 3 minutes of recovery (phase III). After the first session 100 g glucose were administered per os. After 30 minutes blood glucose was measured again and an identical second session was performed with higher blood glucose levels. The Wilcoxon test was used for statistical analysis. During the first session a rise in mean arterial pressure of 22.8 (+/-8.4) mmHg was followed by an arterial vasoconstriction of -6.6 (+/-1.7) %. The administration of 100 g glucose resulted in a significant rise in blood glucose levels within 30 minutes between the two sessions (4.35 mmol/L vs 7.46 mmol/L) (p=0.002). The blood pressure rise of 25.7 (+/-7.3) mm Hg in the second session was associated with a significant loss in arterial vasoconstriction of -2.3 (+/-1.4) % (session I vs session II p=0.002). The myogenic response of the arterial wall in human retinal arterioles was significantly reduced during acute rise of blood glucose levels.

Brief stimulation of the peroneal nerve attenuates the exercise pressor reflex in anaesthetised cats

We recently demonstrated that applying capsaicin to the common peroneal nerve, thereby activating small diameter afferent neurons, caused a substantial rise in mean arterial pressure (MAP) and heart rate (HR) that lasted ∼20 min. In addition, this application of capsaicin transiently attenuated the exercise pressor reflex (EPR). The purpose of the current study was to test the hypothesis that stimulating the peroneal nerve at an intensity that activated both myelinated and unmyelinated axons for a short duration (1 min) causes a similar attenuation of the EPR. Cats were anaesthetised with alpha-chloralose and urethane, the popliteal fossa was exposed, and static contraction was induced by stimulating the tibial nerve. The ipsilateral peroneal nerve was cut and placed on a stimulating electrode. Prior to peroneal nerve stimulation, static contraction of the triceps surae muscle for 1 min increased MAP 48±8 mmHg and HR 16±3 bpm. Electrical stimulation of the central end of the cut peroneal nerve for 1 min (100×motor threshold; 40 Hz; 0.1 ms) increased MAP and HR by 62±11 mmHg and 28±4 bpm, respectively. These increases returned to prestimulation levels within 1 min. Two minutes after the peroneal stimulation was stopped, the EPR was markedly reduced as muscle contraction increased MAP and HR by 20±4 mmHg and 7±2 bpm, respectively. Repeating the muscle contraction ∼25 min after peroneal stimulation increased MAP and HR by 38±8 mmHg and 12±2 bpm, indicating some recovery of the EPR. These results show that brief (1 min) electrical stimulation of afferent neurons in the peroneal nerve attenuates the EPR. This supports the hypothesis that strong activation of small diameter afferent neurons stimulates a nervous system mechanism that diminishes the sensory input from skeletal muscle involved in cardiovascular regulation.

Neuronal Nitric Oxide Synthase Activity in the Paraventricular Nucleus Buffers Central Endothelin-1- induced Pressor Response and Vasopressin Secretion

Endothelin 1 (ET-1) injected into the lateral cerebral ventricle increases sympathetic output, arterial pressure and plasma vasopressin (AVP). These responses are mediated by glutamatergic inputs and inhibited by gamma-amino-butyric acidergic inputs in the paraventricular nucleus (PVN). It has been suggested that nitric oxide enhances these gamma-amino-butyric acidergic inhibitory inputs. The present studies were designed to test the hypothesis that decreasing neuronal nitric oxide synthase (nNOS) activity within the PVN will potentiate ET-1-induced increases in arterial pressure and alter plasma AVP secretion. Male Long Evans rats underwent adenoviral gene transfer of beta-galactosidase, Ad.CMV.beta-gal (6.25 x 10(4) pfu/PVN; control, n = 5) or injection with DNA plasmids encoding dominant-negative forms of nNOS (RSV hemedomain or RSV heme-RedF; mutant, n = 5) having < 8% normal catalytic activity into the PVN bilaterally. Five days post-injection, the baseline mean arterial pressure in conscious rats was similar in both groups: control, 130 +/- 5 mmHg versus mutant, 122 +/- 6 mmHg. The latency of the pressor response observed after lateral cerebral ventricle injection of 10 pmol ET-1 was 4.8 minutes in controls compared with < 1.5 minutes in rats injected with the mutant nNOS (P < 0.05). After ET-1 administration, the average rise in mean arterial pressure was significantly higher in the nNOS mutant group at 1-2 minutes (16.2 +/- 3.5 mmHg versus -0.6 +/- 4.1 mmHg; P < 0.05) as well as 7-10 minutes later (20.2 +/- 5.1 mmHg versus 8 +/- 2.5 mmHg; P < 0.05). Plasma AVP increased from 2.9 +/- 0.7 pg/mL to 11.5 +/- 1.9 pg/mL in controls (P < 0.004) versus 0.3 +/- 0.2 pg/mL to 1.5 +/- 0.9 pg/mL in the mutant group after ET-1. When the residual effect of nitric oxide generated by other nitric oxide synthase isoforms was assessed by injection of 200 microg Nomega-nitro-L-arginine methyl ester bilaterally into the PVN, the mean arterial pressure increased by 12.2 +/- 2.7 mmHg in controls but was almost unchanged in the mutant group (1.8 +/- 2.4 mmHg; P < 0.025 versus control). These results are consistent with the hypothesis that nitric oxide generated by nNOS within the PVN mediates the inhibition of the pressor response to lateral cerebral ventricle ET-1 and that the greater pressor response seen with the dominant-negative nNOS contructs prevents the rise in plasma AVP in baroreflex-intact rats.

Arterial baroreflexes can determine long‐termblood pressure

Arterial baroreflexes can determine long‐termblood pressure

Effect of electroacupuncture on pressor reflex during gastric distension.

The effect of electroacupuncture (EA) on the reflex cardiovascular response induced by mechanical distension of the stomach was studied in ventilated male Sprague-Dawley rats anesthetized by ketamine and alpha-chloralose. Repeated balloon inflation of the stomach to produce 20 mmHg tension on the gastric wall induced a consistent rise in mean arterial pressure, while heart rate (372 +/- 22 beats/min) was unchanged. This response was reversed by transection of the splanchnic nerves. Bilateral application of EA (1-2 mA, 2 Hz) at Neiguan-Jianshi acupoints (pericardial meridian, Pe 5-6) over the median nerve for 30 min significantly decreased the pressor response from 33 +/- 6 to 18 +/- 4 mmHg (n = 7, P < 0.05). This effect began after 10 min of EA and continued for 40 min after termination of EA. EA at Zusanli-Shangquxu acupoints (stomach meridian, St 36-37) over the deep peroneal nerve similarly inhibited the pressor response. The effect lasted for 10 min after EA was stopped (n = 6, P < 0.05), while EA at Guangming-Xuanzhong acupoints (gallbladder meridian, GB 37-39) over the superficial peroneal nerve did not inhibit the pressor response. Naloxone injected intravenously (n = 6) immediately after termination of EA or administered by microinjection into the rostral ventrolateral medulla (rVLM) 25 min after initiation of EA (n = 6) reversed the inhibition by EA, suggesting an opiate mechanism, including the rVLM, was involved.

Pigs are not a reliable experimental model in the study of the haemodynamic and respiratory effects of CO2 pneumoperitoneum.

Haemodynamic and respiratory effects of a CO2 pneumoperitoneum (intra-abdominal pressure = 12 mmHg) associated to a head-up position(15 degrees ) were studied in 20 pigs using a Swan-Ganz catheter and the Single Breath Test for CO2. The pneumoperitoneum induced a moderate rise in mean arterial pressure (+17%) (P<0.001) without any variation in heart rate, cardiac output and systemic vascular resistances. The following respiratory effects were observed: an increase in PaCO2 (+20%) (P<0.001), PE'CO2 (+31%) (P<0.001), expired volume of CO2 (+28%) (P<0.001), arterial to end-tidal CO2 gradient (+80%) (P<0.001) and alveolar dead space (+40%) (P<0.001) occured. Alveolar ventilation remained stable. Finally and contrary to healthy human patient, intraperitoneal CO2 insufflation in pig induced slight haemodynamic changes and major respiratory modifications. Thus, our data do not support the conclusion that the pig is a reliable experimental model for studying the pathophysiology of CO2 pneumoperitoneum-induced changes in haemodynamic and respiratory parameters, in human patients.

Effect of cold on fetal heart rate and its variability.

1. The effects of cold saline (25 mL) injected over the fetal skin on fetal heart rate (HR) and HR variability (HRV), measured as the coefficient of variation (CV) in pulse interval (PI) and by power spectral analysis (PSA), were measured in 10 chronically catheterized fetal sheep aged 140-144 days. To determine the extent to which effects on HR and HRV were mediated by the sympathoadrenal neuroendocrine axis and the cardiac vagus, experiments were performed before and after beta-adrenoreceptor blockade with propranolol (n = 12 fetuses) or before and after cardiac vagal blockade with atropine (n = 4 fetuses). 2. Injection of ice-cold saline over the skin caused an immediate rise in mean arterial pressure (MAP) from 46+/-1 to 55+/-1 mmHg (P < 0.001) and HR from 156+/-2 to 182+/-2 b.p.m. (P < 0.001). Heart rate variability, measured as CV of PI, rose from 3.5+/-0.2 to 8.0+/-0.2% (P < 0.001) and total power spectral density (PSD) increased from 78+/-6 to 278+/-16 units (P < 0.001) as measured by PSA. Within 100s, MAP, HR and HRV had returned to baseline. 3. Beta-adrenoreceptor blockade abolished all these changes in HR, HRV and PSD, but had no effect on changes in MAP. Atropine had no demonstrable effect on the responses to cold. 4. Therefore, the increase in fetal MAP, HR and HRV that occurred with stimulation of peripheral thermoreceptors was the result of increased activity of the sympathetic nervous system. Alterations in efferent cardiac vagal tone were not involved in the cardiac response to cold.

Conditioned fear to environmental context: cardiovascular and behavioral components in the rat

This study compares the time course of the cardiovascular changes (mean arterial blood pressure, heart rate) and behavioral changes (freezing, rearing, grooming and activity) evoked by 30 min long exposures to a footshock chamber before and after conditioning with footshocks. The main finding is that the conditioned fear evoked by re-exposure to the footshock chamber after conditioning is associated with a prolonged freezing response, a marked rise in mean arterial pressure (+35 mm Hg above a resting baseline of 105 mm Hg) and a delayed rise in heart rate. The pattern of behavioral and cardiovascular changes is the same as with conditioned fear to a discrete stimulus but the effect is a lot longer.

Increase in renal medullary nitric oxide synthase activity protects from norepinephrine-induced hypertension.

Studies were performed in conscious Sprague-Dawley rats to determine the role of the alpha(2)-adrenergic receptor-mediated increase in the renal medullary nitric oxide synthase (NOS) activity as a counterregulatory mechanism of blood pressure control in response to increased renal adrenergic stimulation. A subpressor dose of norepinephrine (NE, 8 microg. kg(-1). h(-1)) was infused intravenously, and NOS activity was determined with arginine-citrulline conversion by high-performance liquid chromatography in renal cortical and outer and inner medullary tissues. It was found that after 7 days of intravenous NE infusion, NOS activity was significantly higher in both the outer and inner medullary tissues (158+/-45 versus 30+/-24 pmol. mg(-1). h(-1) [outer medulla] and 5.1+/-0.7 versus 2.0+/-0.5 nmol. mg(-1). h(-1) [inner medulla] for NE-treated versus control rats, respectively). To determine whether the increase of NOS activity was mediated through renal medullary alpha(2)-receptors, the receptor antagonist rauwolscine (RAU, 1 microg. kg(-1). min(-1)) was infused via an implanted renal medullary interstitial catheter, and the consequences of intravenous NE administration were evaluated. NOS activity was significantly lower in the RAU-infused animals and did not increase with infusion of NE. To determine the systemic effects of the renal medullary alpha(2)-receptors, studies were performed to determine the consequences of chronic intravenous infusion of subpressor amounts of NE in the presence and absence of renal medullary alpha(2)-receptor inhibition. Under conditions in which RAU was continuously infused into the renal medulla, the same subpressor dose of NE caused sustained and reversible hypertension (mean arterial pressure increased from 120+/-3 to 131+/-3 mm Hg). Chronic blunting of the renal medullary NOS activity with N(G)-nitro-L-arginine methyl ester (75 microg. kg(-1). h(-1)) also enabled NE to produce a significant rise in mean arterial pressure (from 117+/-2 to 134+/-4 mm Hg). We conclude that the hypertensive effects of moderate elevations of renal adrenergic activity were chronically buffered by the alpha(2)-receptor-mediated increase in NOS activity within the renal medulla.

Serial changes in cardiovascular and renal function of rabbits ingesting a high-fat, high-calorie diet

To explore the mechanisms of obesity-induced hypertension we analyzed the sequential changes in cardiovascular and renal function in adult rabbits switched to high-fat diet (HFD) for 8 weeks. Animals were housed in metabolic cages for continuous 24-h recording of arterial pressure by telemetry and daily urine collection. High-fat diet induced a progressive increase in body weight (+47%) and a rapid rise in mean arterial pressure, heart rate, and glomerular filtration rate that stabilized, respectively, at 14%, 31% and 68% greater than control values. Time-course analysis of changes in blood pressure may reveal two components of obesity-induced hypertension, an early phase related to HFD itself and a later phase related to weight gain.

Characterization of acute reversible systemic hypertension in a model of heme protein-induced renal injury.

In the glycerol model of renal injury we describe an acute rise in systemic arterial pressure which is attended by a reduced vasodilatory response to acetylcholine in vivo; vasodilatory responses to verapamil, however, were not impaired. Neither arginine nor sodium nitroprusside diminished this rise in blood pressure; N(omega)-nitro-L-arginine methyl ester (L-NAME) elevated basal mean arterial pressure and markedly blunted the rise in mean arterial pressure following the administration of glycerol. Aortic rings from the glycerol-treated rat demonstrate an impaired vasodilatory response to acetylcholine, an effect not repaired by arginine; the vasodilatory responses to nitric oxide donors, sodium nitroprusside and SIN-1, were also impaired; 8-bromo-cGMP, at higher doses, evinced a vasodilatory response comparable to that observed in the control rings. This pattern of responses was not a nonspecific effect of aortic injury, since aortic rings treated with mercuric chloride, a potent oxidant, displayed an impaired vasodilatory response to acetylcholine but not to sodium nitroprusside. We conclude that in the glycerol model of heme protein-induced tissue injury, there is an acute elevation in mean arterial pressure attended by impaired endothelium-dependent vasodilatation in vitro and in vivo. We suggest that the acute scavenging of nitric oxide by heme proteins depletes the blood vessel wall of its endogenous vasodilator and permeation of heme proteins into the blood vessel wall may contribute to such sustained effects as observed in vitro.

Failure of acute hyperinsulinemia to alter blood pressure is not due to baroreceptor feedback

It is well documented that acute insulin administration stimulates the sympathetic nervous system in both humans and animals. Despite marked sympathetic activation during acute hyperinsulinemia, blood pressure is generally not increased because it is overridden by the vasodilator action of insulin. The maintenance of blood pressure in the face of sympathetic activation is unknown. A possible mechanism includes feedback regulation by the baroreceptor reflex arc. In normotensive states, hyperinsulinemic-induced sympathetic activation may tend to elevate blood pressure, but this change is rapidly sensed by the baroreceptors in the carotid arteries (and aortic arch), and a counterbalancing increase in vasodilation could return blood pressure to normal. Thus, it can be speculated that, in the event of diminished baroreceptor sensitivity and suppressed vasodilator actions of insulin, common abnormalities in hypertension, acute insulin infusion would be expected to increase blood pressure. We undertook the present study to determine whether the baroreceptor reflex arc modulated the blood pressure response to acute hyperinsulinemia. To this end, six normotensive dogs underwent saline or insulin infusions before and after deactivation of the carotid and aortic baroreceptors. Baroreceptor dysfunction was documented after denervation in all cases by an abnormal response to phenylephrine injections. Before denervation, insulin infusions caused a slight but nonsignificant rise in mean arterial pressure (MAP; 110 ± 5 to 120 ± 5 mm Hg; P = 0.13). Baroreceptor denervation caused a marked variability in blood pressure. However, basal mean arterial pressure was not significantly altered. Neither saline nor insulin infusions (105 ± 10 v 105 ± 8 mm Hg, basal v steady state) caused a significant change in MAP in denervated dogs. Likewise, insulin and saline did not change heart rates significantly in intact or denervated animals. Furthermore, glucose metabolism was similar in both groups of animals. This study demonstrates that the baroreceptor reflex arc does not mediate the blood pressure response to acute hyperinsulinemia.

Induced hypothermia as salvage treatment for refractory cardiac failure following paediatric cardiac surgery.

Following corrective cardiac surgery in infants and children for congenital heart disease, a persistent low cardiac output refractory to conventional modes of treatment is associated with a mortality approaching 100%. We advocate the use of whole body hypothermia to reduce tissue oxygen demand and provide a degree of cellular protection against ischaemia allowing time for recovery. We describe our experience. Between July 1986 and December 1995, 1885 infants and children underwent surgery (operative mortality, 6%), 1302 requiring cardiopulmonary bypass. Fifty-seven patients had a persistent low cardiac output, impaired respiratory function, decreased urine output and acidosis despite maximal intensive care treatment. Cooling to 32-33 degrees C was therefore started using a thermostatically controlled water filled cooling blanket. Following cooling, there was a fall in heart rate (P<0.001), a rise in mean arterial pressure (P<0.001) and a fall in mean atrial pressure (P<0.001). Significant (P<0.001) increases in pH and urine output were also recorded. Thirty-one (54%) of the 57 patients treated with cooling survived to leave hospital. No long-term sequelae have been noted in these patients. Induced hypothermia is a useful salvage treatment, in children following corrective cardiac surgery when all conventional treatment has been tried and failed.

Failure of acute hyperinsulinemia to alter blood pressure is not due to baroreceptor feedback

It is well documented that acute insulin administration stimulates the sympathetic nervous system in both humans and animals. Despite marked sympathetic activation during acute hyperinsulinemia, blood pressure is generally not increased because it is overridden by the vasodilator action of insulin. The maintenance of blood pressure in the face of sympathetic activation is unknown. A possible mechanism includes feedback regulation by the baroreceptor reflex arc. In normotensive states, hyperinsulinemic-induced sympathetic activation may tend to elevate blood pressure, but this change is rapidly sensed by the baroreceptors in the carotid arteries (and aortic arch), and a counterbalancing increase in vasodilation could return blood pressure to normal. Thus, it can be speculated that, in the event of diminished baroreceptor sensitivity and suppressed vasodilator actions of insulin, common abnormalities in hypertension, acute insulin infusion would be expected to increase blood pressure. We undertook the present study to determine whether the baroreceptor reflex arc modulated the blood pressure response to acute hyperinsulinemia. To this end, six normotensive dogs underwent saline or insulin infusions before and after deactivation of the carotid and aortic baroreceptors. Baroreceptor dysfunction was documented after denervation in all cases by an abnormal response to phenylephrine injections. Before denervation, insulin infusions caused a slight but nonsignificant rise in mean arterial pressure (MAP; 110 ± 5 to 120 ± 5 mm Hg; P = 0.13). Baroreceptor denervation caused a marked variability in blood pressure. However, basal mean arterial pressure was not significantly altered. Neither saline nor insulin infusions (105 ± 10 v 105 ± 8 mm Hg, basal v steady state) caused a significant change in MAP in denervated dogs. Likewise, insulin and saline did not change heart rates significantly in intact or denervated animals. Furthermore, glucose metabolism was similar in both groups of animals. This study demonstrates that the baroreceptor reflex arc does not mediate the blood pressure response to acute hyperinsulinemia. Am J Hypertens 1999;12:405–413 © 1999 American Journal of Hypertension, Ltd.

EndothelinBreceptors are functionally important in mediating vasoconstriction in the systemic circulation in patients with left ventricular systolic dysfunction

OBJECTIVESThis study was designed to assess the functional importance of endothelin (ET)Breceptors in patients with left ventricular systolic dysfunction (LVSD) by comparing the hemodynamic effects of ET-1, a nonselective ETAand ETBagonist, with ET-3, a selective ETBreceptor agonist.BACKGROUNDKnowledge of the functional importance of ETBreceptors in mediating vasoconstriction in chronic heart failure will help determine whether antagonists at both ETAand ETBreceptors are required to fully prevent vasoconstriction to endogenously produced ET-1.METHODSWe infused ET-1 (5 and 15 pmol/min) and ET-3 (5 and 15 pmol/min) into two separate groups of eight patients with LVSD with similar baseline hemodynamic indices. Hemodynamics were measured using a pulmonary thermodilution catheter and an arterial line.RESULTSEndothelin-1 infusion led to systemic vasoconstriction, with a rise in mean arterial pressure (mean ± SEM 100 ± 3 to 105 ± 3 mm Hg, p < 0.02) and systemic vascular resistance (1,727 ± 142 to 2,055 ± 164 dyn/s/cm−5, p < 0.001) and a fall in cardiac index (2.44 ± 0.21 to 2.22 ± 0.20 liters/min/m2, p < 0.01). Endothelin-3 infusion also led to systemic vasoconstriction, with a rise in mean arterial pressure (99 ± 6 to 105 ± 6 mm Hg, p < 0.01) and systemic vascular resistance (1,639 ± 210 to 1,918 ± 245 dyn/s/cm−5, p < 0.01) and a fall in cardiac index (2.66 ± 0.28 to 2.42 ± 0.24 liters/min/m2, p < 0.05). Pulmonary hemodynamic measurements did not change significantly in either group.CONCLUSIONSBoth ET-1 and ET-3 infusions led to systemic vasoconstriction; the hemodynamic changes observed were of a similar magnitude at the same molar concentration. This suggests that ETBreceptors are functionally important in mediating vasoconstriction, at least in the systemic circulation, in patients with LVSD.