Doppler Ultrasonic Flow Probes Research Articles

Hypertension in Primary Aldosteronism Is Initiated by Salt-Induced Increases in Vascular Resistance With Reductions in Cardiac Output.

Few studies have investigated the hemodynamic mechanism whereby primary aldosteronism causes hypertension. The traditional view holds that hyperaldosteronism initiates hypertension by amplifying salt-dependent increases in cardiac output (CO) by promoting increases in sodium retention and blood volume. Systemic vascular resistance (SVR) is said to increase only as a secondary consequence of the increased CO and blood pressure. However, mounting evidence indicates that aldosterone can influence multiple pathways regulating vascular tone. We investigated the primary hemodynamic mechanism whereby hyperaldosteronism promotes salt sensitivity and initiation of salt-dependent hypertension. In unilaterally nephrectomized male Sprague-Dawley rats given infusions of aldosterone or vehicle, we used chronically implanted arterial pressure probes and Doppler ultrasonic flow probes to continuously monitor changes in mean arterial pressure, CO, and SVR 24 hours/day, 7 days/week in response to increases in salt intake. In vehicle-treated control rats, switching from a low-salt diet to a high-salt diet initiated modest increases in mean arterial pressure by increasing SVR while simultaneously decreasing heart rate and CO. In aldosterone-treated rats compared with control rats, switching from a low-salt diet to a high-salt diet initiated significantly greater increases in mean arterial pressure and SVR and significantly greater decreases in heart rate and CO. Aldosterone promoted salt sensitivity and initiation of salt-dependent hypertension by amplifying salt-induced increases in SVR while decreasing CO. Increases in CO are not required for the initiation or maintenance of hypertension. These findings challenge the traditional view of the hemodynamic mechanisms that cause hypertension in primary aldosteronism.

Effectiveness of intravenous fluid resuscitation in hypotensive cats: 82 cases (2012-2019).

To evaluate the effectiveness of intravenous fluid resuscitation in hypotensive cats in an emergency room setting. Secondary objectives were to investigate changes in heart rate (HR) and body temperature (BT) in response to fluid resuscitation, and the association of these changes with patient survival. Retrospective study. University teaching hospital. Eighty-two cats with confirmed hypotension. None. Medical records from 2012 to 2019 were searched for cats that had documented systemic arterial hypotension (blood pressure measured using a Doppler ultrasonic flow probe [DBP]<90mm Hg) on presentation to the emergency room. Data collected included patient characteristics and DBP, HR, and BT before and after fluid resuscitation, type and volume of fluids administered, and outcome. The median DBP before and after resuscitative fluid therapy in all cats was 65mm Hg (range, 20-85mm Hg) and 80mm Hg (range, 20-128mm Hg), respectively (P<0.001). However, only 30 cats (37%) were classified as responders to fluid resuscitation (DBP≥90mm Hg following bolus therapy). The mean HR and median BT before resuscitative fluid therapy was 159/min and 36.7°C. Following fluid resuscitation, where measured, the mean HR and median BT was 154/min (P=1.00) and 35.9°C (P=1.00). No significant differences in HR and BT were identified between responders and non-responders. Cats had a low survival rate of 7%. All survivors (n=5) were initially bradycardic (HR<160/min), compared to only 45% of non-survivors (P=0.4). Bolus fluid resuscitation effectively increases blood pressure in hypotensive cats; however, it does not result in normalization of blood pressure, HR, or BT in the majority of cases.

Cardiac output, at rest and during exercise, before and during myocardial ischemia, reperfusion, and infarction in conscious mice

Multiple systems and regulatory strategies interact to control cardiac homeostasis. In fact, regulated systems, feedback controls, and redundant control mechanisms dominate in whole animals. Accordingly, molecular and cellular tools and techniques must be utilized in complex models with multiple systems and regulatory strategies to fully appreciate the physiological context. Currently, these techniques are mainly performed under conditions remote from the normal in vivo condition; thus, the extrapolation of molecular changes to the in vivo situation and the facilitation of translational aspect of the findings are limited. A major obstacle has been the reliance on preparations that do not mimic the clinical or physiological situation. This is particularly true regarding measurements of cardiac function in mice. To address these concerns, we used a permanently implanted Doppler ultrasonic flow probe on the ascending aorta and coronary artery occluder for repeated measurements of ascending aortic blood flow (cardiac output) in conscious mice, at rest and during exercise, before and during coronary artery occlusion/reperfusion and infarction. The conscious mouse model permits detailed monitoring of within-animal changes in cardiac function during myocardial ischemia, reperfusion, and infarction in an intact, complex model free of the confounding influences of anesthetics, surgical trauma, and restraint stress. Results from this study suggest that previous protocols may have overestimated resting baseline values and underestimated cardiac output reserve. Using these procedures in currently available spontaneous or engineered mouse mutants has the potential to be of major importance for advancing the concepts and methods that drive cardiovascular research.

Partial hindlimb occlusion reduced the susceptibility to sustained ventricular tachycardia in conscious rats.

Remote conditioning induced by ischemia in distant organs protects the heart from ischemia/reperfusion injury; however, its effect on ischemia-induced ventricular arrhythmias is unknown. Therefore, we tested the hypothesis that partial hindlimb occlusion during coronary artery occlusion increases the ventricular arrhythmia threshold (VAT) induced by coronary artery occlusion. Rats (n = 7) were instrumented with a radio-telemetry device for recording arterial pressure, electrocardiogram (ECG), and body temperature. A Doppler ultrasonic flow probe and vascular occluder were placed around the terminal aorta. Finally, a snare was placed around the left main coronary artery. The VAT was determined without and, on an alternate day, during partial hindlimb occlusion (remote conditioning) in conscious rats. Without remote conditioning, the VAT was 4.56 + 0.15 minutes. Importantly, remote conditioning significantly increased the VAT (6.29 + 0.49 minutes), suggesting that ischemia in a distant organ may delay the development of ischemia-induced ventricular arrhythmias.

Sympathetic cutaneous vasomotor alerting responses (SCVARs) are associated with hippocampal theta rhythm in non-moving conscious rats

Alerting stimuli that cause sympathetic cutaneous vasomotor alerting responses (“SCVARs”) in the thermoregulatory vascular bed of the rabbit ear pinna also induce theta (5–8 Hz) rhythm in the hippocampal EEG, a marker that the animal is engaged with the environment. The present study determines the relation between SCVARs in the thermoregulatory tail artery vascular bed and hippocampal EEG theta rhythm in Sprague-Dawley rats. A Doppler ultrasonic flow probe chronically implanted around the base of the tail artery was used to measure SCVARs. Unipolar electrodes were implanted in the hippocampus (CA1 region) to measure EEG. Six standard non-noxious brief alerting stimuli were administered during continuous recording of tail blood flow and EEG. The SCVAR index was calculated as the percentage fall from pre-alerting blood flow values. After stimuli the SCVAR index for the tail artery blood flow was 84 ± 2% of the pre-alerting control. In contrast, the same stimuli caused little fall in blood flow within the superior mesenteric bed (SCVAR index = 18 ± 2%). The proportion of theta power in the total frequency range (0–20 Hz) increased significantly after alerting stimuli (46 ± 2% vs. 29 ± 1% before stimuli, p < 0.05). Theta proportion began to increase approximately 0.5 s after the stimuli and preceded SCVARs by approximately 1 s. The SCVAR index was correlated with the magnitude of the increment in theta power. Our study demonstrates that alerting responses resulting in selective vasoconstriction of the tail vascular bed are associated with hippocampal theta rhythm in conscious rats.

Partial hindlimb occlusion during coronary artery occlusion reduces the susceptibility to ventricular arrhythmias via the intrinsic adenosine receptor system in conscious rats

Temporary occlusion of coronary arteries can lead to potentially lethal arrhythmias. The arrhythmias are triggered directly by ischemia or during the reperfusion phase. Remote conditioning induced by ischemia in distant organs protects the heart from ischemic/reperfusion injury. However, the effect of remote conditioning on ischemia‐induced ventricular arrhythmias is unknown. Therefore, we tested the hypothesis that partial hindlimb occlusion during coronary artery occlusion reduces the susceptibility to ventricular arrhythmias. To test this hypothesis, 7 rats were instrumented for recording arterial pressure and ECG. A Doppler ultrasonic flow probe and vascular occluder were placed around the terminal aorta. Finally, a snare was placed around the left main coronary artery. The response to coronary artery occlusion during partial hindlimb occlusion was determined in conscious rats. Occlusion of the left main coronary artery resulted in tachy‐arrhythmias that culminated in ventricular fibrillation within 4.56 ± 0.15 min. Partial hindlimb occlusion during coronary artery occlusion culminated in ventricular fibrillation within 6.29 ± 0.49 min. Adenosine receptor blockade (theophylline, 10 mg/kg) attenuated the cardioprotective effects of remote conditioning (4.62 ± 0.79 min). Supported by HL67713

Sex differences to myocardial ischemia and β-adrenergic receptor blockade in conscious rats

We recently documented sex differences in the susceptibility to reperfusion-induced sustained ventricular tachycardia and beta-adrenergic receptor blockade in conscious rats. However, the effect of sex on ischemia-induced ventricular arrhythmias and beta-adrenergic receptor blockade is under-investigated. Therefore, we tested the hypothesis that gonadal hormones influence the ventricular arrhythmia threshold (VAT) induced by coronary artery occlusion as well as the response to beta-adrenergic receptor blockade. The VAT was defined as the time from coronary occlusion to sustained ventricular tachycardia resulting in a reduction in arterial pressure. Male and female intact and gonadectomized (GnX) rats were instrumented with a radiotelemetry device for recording arterial pressure, temperature, and ECG, as well as a Doppler ultrasonic flow probe to measure cardiac output and a snare around the left main coronary artery. The VAT was determined in conscious rats by pulling on the snare. The VAT was significantly longer in intact females (5.56 +/- 0.19) vs. intact males (4.31 +/- 0.14 min). This sex difference was abolished by GnX. Specifically, GnX decreased the VAT in females (4.55 +/- 0.22) and increased the VAT in males (5.14 +/- 0.30 min). Thus male sex hormones increase and female sex hormones decrease the susceptibility to ischemia-induced sustained ventricular tachycardia. beta-Adrenergic receptor blockade increased the VAT in intact males and GnX females only. Thus gonadal hormones influence the response to beta-adrenergic receptor blockade. Uncovering major differences between males and females in the pathophysiology of the cardiovascular system may result in sex-specific optimization of patient treatments.

Application of Doppler Ultrasonography in Cattle Reproduction

The development of Doppler processing extended the scope of sonographic imaging from an anatomical to a physiological basis. This technique became established as a clinical tool in human gynaecology. For example, it has been discussed that the implantation of an embryo is influenced by the uterine blood flow. In cows, this uterine blood flow was investigated, using surgically implanted Doppler ultrasonic or electromagnetic blood flow probes prior to the introduction of colour Doppler sonography in bovine medicine. Therefore, the aims of our studies were to use transrectal Doppler sonography for the non-invasive measurement of uterine and ovarian blood flow in cows and to determine changes in genital perfusion during the oestrous cycle, pregnancy and puerperium, respectively. The results of our studies show that transrectal flow imaging can be used to obtain blood flow velocity waveforms from the uterine arteries at any time during the oestrous cycle, pregnancy and puerperium. During all these phases, characteristic changes in the uterine blood flow could be observed. This uterine blood flow was low during diestrus and high during proestrus and oestrus. During pregnancy, an exponential rise in uterine blood supply could be detected. There was a positive relationship between the uterine blood flow volume (BFV) at the end of gestation and the birth weight of calves. During puerperium, the uterine BFV declined tremendously, especially during the first week after birth. In cows, with pathological disturbances of the pueperium a delayed decrease in the uterine BFV was observed. Characteristic alterations occurred also in the luteal blood flow during the oestrous cycle, which were highly related to those of the progesterone levels. Furthermore, it has been detected by the colour Doppler technique that there is no decrease, but an increase of the luteal blood flow at the beginning of luteolysis in cows. Another group has found that there are close relationships between the LH-surge and the follicular blood flow before ovulation. In conclusion, these studies show that transrectal colour Doppler sonography is a useful technique for the investigation of the genital blood flow and provides new information about physiological changes of the genital organs during, all reproductive phases. The influence of the genital blood flow on fertility in cows needs to be examined further in future studies.

Activation of dopamine D 2 receptors in the CNS inhibits sympathetic cutaneous vasomotor alerting responses (SCVARs), contributing to clozapine's SCVAR-inhibiting action

Sympathetic neural outflow to thermoregulatory cutaneous vascular beds is selectively activated when the individual is aroused, so that cutaneous blood flow is characterized by sudden alerting-related falls to near zero levels (“SCVARs”, sympathetic cutaneous vasomotor alerting responses). Our previous work shows that clozapine, an atypical antipsychotic drug used in schizophrenia, profoundly inhibits SCVARs. Clozapine, conventionally assumed to have a dopamine D 2 receptor antagonist action, also increases baseline cutaneous blood flow and lowers body temperature. However dopamine D 2 receptor agonists lower temperature, suggesting that a dopamine D 2 agonist action might also reduce SCVARs. The present study determined whether a dopamine D 2 agonist action contributes to clozapine's SCVAR-inhibiting effect. SCVARs were measured in conscious rats with a Doppler ultrasonic flow probe chronically implanted around the base of the artery, with probe wires passing subcutaneously to a headpiece. Doppler signals were monitored via a flexible connection between the headpiece and a swivel device in the roof of the cage. Apomorphine (0.1–0.5 mg/kg), quinpirole (0.05–0.25 mg/kg) and 7-OH-DPAT (0.02–0.5 mg/kg) dose-dependently reduced SCVARs. Pre-treatment with the dopamine receptor antagonist spiperone (20 μg/kg) but not the D 1 antagonist SCH-23390 or the peripheral dopamine D 2 antagonist domperidone, abolished this effect. Spiperone pre-treatment reduced the SCVAR-inhibiting action of clozapine (0.06–1.0 mg/kg). Chlorpromazine (0.1–10 mg/kg) also dose-dependently inhibited SCVARs, but this effect was not reduced by pre-treatment with spiperone. Mechanisms underlying clozapine's SCVAR-inhibiting effect include dopamine D 2 receptor agonism, not dopamine D 2 receptor antagonism, calling into question the mechanism of the drug's therapeutic action in schizophrenia.

Ovariectomy Reduces the Arrhythmia Threshold Induced by Coronary Artery Occlusion in Conscious Rats

Sudden cardiac death is the leading cause of death for men and women in industrially developed countries. The majority of these deaths result from tachyarrhythmias that culminate in ventricular fibrillation. Approximately 1% of the victims of cardiac arrest are resuscitated and survive to leave the hospital. Importantly, there are gender differences in cardiac physiology and in the types and severity of cardiac arrhythmias. Female sex hormones may be a contributing factor. Therefore, we tested the hypothesis that ovariectomy reduces the arrhythmia threshold induced by coronary artery occlusion. Female Wistar rats were ovariectomized or sham ovariectomized and instrumented with a radio-telemetry device for recording arterial pressure, ECG and body temperature. Six weeks later a Doppler ultrasonic flow probe was placed around the ascending aorta to measure cardiac output and a snare was placed around the left main coronary artery. After recovery, the response to coronary artery occlusion was determined in conscious intact and ovariectomized rats by pulling on the snare. Occlusion of the left main coronary artery in intact females resulted in tachyarrhythmias that culminated in ventricular fibrillation within 3.7 +/− 0.1 min. In contrast, occlusion of the left main coronary artery in ovariectomized females resulted in tachyarrhythmias that culminated in ventricular fibrillation within 2.4 +/− 0.1 min. These responses were associated with differences in cardiac autonomic tonus and electrophysiology. Supported by HL67713

5-hydroxytryptamine 2A receptors regulate sympathetic nerves constricting the cutaneous vascular bed in rabbits and rats

Hyperthermia induced by 3,4-methylenedioxymethamphetamine (MDMA) is partially due to sympathetically-mediated cutaneous vasoconstriction that impairs normal heat dissipation. MDMA acts by releasing monoamines, including 5-hydroxytryptamine (5-HT), but receptor mechanisms underlying MDMA-elicited hyperthermia and cutaneous vasoconstriction are not known. The specific 5-HT2A agonist (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) is a potent hallucinogen that also causes marked hyperthermia, suggesting the possibility that DOI, via stimulation of 5-HT2A receptors, might also cause sympathetically mediated cutaneous vasoconstriction. We tested this hypothesis in conscious unrestrained rabbits and rats. Blood flow was assessed by chronically implanted Doppler ultrasonic flow probes. Body temperature was measured by i.p. telemetric probes. We compared effects of DOI on cutaneous blood flow (ear pinna in rabbits, tail in rats) with effects on mesenteric blood flow and arterial pressure. Hyperthermia induced by DOI (5–100 μg/kg i.v. in rabbits and 100 μg/kg s.c. in rats) was preceded and accompanied by markedly reduced blood flow to the cutaneous bed, with no change in flow to the mesenteric bed. In rabbits, DOI (5 μg/kg i.v.) did not affect arterial pressure or heart rate. DOI (100 μg/kg i.v.) caused a moderate rise in arterial pressure. In rabbits, the 5-HT2A receptor antagonists ketanserin (0.3 mg/kg i.v.) and AC90179 (0.5 mg/kg i.v.) reversed the ear pinna vasoconstriction induced by DOI (5 μg/kg i.v.). In rats, ketanserin (3 mg/kg s.c.) reversed tail vasoconstriction and hyperthermia induced by DOI (100 μg/kg s.c.). In rabbits, the cutaneous vasoconstricting effect of DOI (5 μg/kg i.v.) was substantially abolished in the ipsilateral ear pinna after interruption of preganglionic sympathetic nerve activity by unilateral section of the cervical sympathetic trunk. Thus hyperthermia evoked by direct stimulation of 5-HT2A receptors is associated with marked sympathetically mediated vasoconstriction, selective for the cutaneous bed. Impairment of the ability to dissipate heat following drug-induced stimulation of 5-HT2A receptors is likely to contribute to hyperthermia induced by MDMA and by hallucinogenic drugs such as LSD.

Postexercise alpha-adrenergic receptor hyporesponsiveness in hypertensive rats is due to nitric oxide.

We tested the hypothesis that a single bout of dynamic exercise produces a postexercise hypotension (PEH) and alpha(1)-adrenergic receptor hyporesponsiveness in spontaneously hypertensive rats (SHR). The postexercise alpha(1)-adrenergic receptor hyporesponsiveness is due to an enhanced buffering of vasoconstriction by nitric oxide. Male (n = 8) and female (n = 5) SHR were instrumented with a Doppler ultrasonic flow probe around the femoral artery. Distal to the flow probe, a microrenathane catheter was inserted into a branch of the femoral artery for the infusion of the alpha(1)-adrenergic receptor agonist phenylephrine (PE). A microrenathane catheter was inserted into the descending aorta via the left common carotid artery for measurements of arterial pressure (AP) and heart rate. Dose-response curves to PE (3.8 x 10(-3) - 1.98 x 10(-2)microg/kHz) were generated before and after a single bout of dynamic exercise. Postexercise AP was reduced in male (13 +/- 3 mmHg) and female SHR (18 +/- 7 mmHg). Postexercise vasoconstrictor responses to PE were reduced in males due to an enhanced influence of nitric oxide. However, in females, postexercise vasoconstrictor responses to PE were not altered. Results suggest that nitric oxide- mediated alpha(1)-adrenergic receptor hyporesponsiveness contributes to PEH in male but not female SHR.

SINO-AORTIC DENERVATION ALTERS THE HEMODYNAMIC RESPONSE TO EXERCISE IN HYPERTENSIVE RATS

The effect of sino-aortic denervation (SAD) on the heart rate (HR), arterial pressure (AP) and regional blood flow responses during dynamic exercise was examined in spontaneously hypertensive rats (SHR). Intact (n = 14) and SAD (n = 17) rats were instrumented with arterial catheters and mesenteric and iliac Doppler ultrasonic flow probes. After recovery, all rats underwent a graded exercise test. Heart rate increased significantly during exercise in intact and SAD rats. There was no significant difference in the steady state heart rate response to exercise in the intact and SAD rats. Arterial pressure increased during exercise in the intact rats. In sharp contrast, arterial pressure decreased during exercise in the SAD rats. Iliac vascular conductance increased during exercise in the intact and SAD rats. The increase in iliac vascular conductance during exercise was significantly greater in the SAD rats. Mesenteric vascular conductance decreased during exercise in the intact and SAD rats. The decrease in mesenteric vascular conductance during exercise was significantly attenuated in the SAD rats. Results suggest that functioning arterial baroreceptors are required for the typical hemodynamic responses during dynamic treadmill running in hypertensive rats.

Arterial baroreflex regulation of regional vascular conductance at rest and during exercise.

We tested the hypothesis that dynamic exercise resets the operating point and attenuates the spontaneous gain of the arterial baroreflex regulation of mesenteric and hindlimb vascular conductance in hypertensive rats. Eleven adult male spontaneously hypertensive rats were chronically instrumented with left carotid arterial catheters and Doppler ultrasonic flow probes around the superior mesenteric and left common iliac arteries. After the rats recovered, arterial baroreflex function was examined by recording reflex changes in conductance in response to spontaneous changes in mean arterial pressure before exercise and during steady-state treadmill running at 6 and 18 m/min. Dynamic exercise reduced the spontaneous baroreflex gain of mesenteric conductance (by 51 and 36%) and maximum mesenteric conductance (by 24 and 32%) at 6 and 18 m/min, respectively. In sharp contrast, dynamic exercise increased the spontaneous maximum iliac conductance (by 32 and 47%) without changing the spontaneous gain. Sinoaortic denervation eliminated the relationship between mean arterial pressure and conductance by reducing the mesenteric (92%) and iliac (68%) vascular conductance gain. These results demonstrate that dynamic exercise has differential effects on the regulation of mesenteric and iliac vascular conductance in hypertensive rats.

Postexercise hypotension is mediated by reductions in sympathetic nerve activity.

Mean arterial pressure (MAP), the product of cardiac output (CO) and total peripheral resistance (TPR), is reduced below preexercise levels after a single bout of mild to moderate dynamic exercise. Thus acute, dynamic exercise may be used as a safe, therapeutic approach to reduce MAP. However, the mechanisms responsible for the postexercise hypotension (PEH) are unknown. We tested the hypothesis that PEH is associated with reductions in TPR and sympathetic nerve activity (SNA). Two experimental protocols were designed to test this hypothesis in male spontaneously hypertensive rats (SHR). In protocol 1 (n = 9), CO and TPR were determined before, during, and after exercise. In protocol 2 (n = 7), lumbar SNA (LSNA) was recorded before and after exercise. Rats in protocol 1 were chronically instrumented with left carotid arterial catheters and ascending aortic Doppler ultrasonic flow probes. Rats in protocol 2 were chronically instrumented with left carotid arterial catheters and electrodes around the lumbar sympathetic trunk. Dynamic treadmill exercise (9-12 m/min, 10% grade for 40 min) resulted in a postexercise reduction in MAP (from 143 +/- 5 to 128 +/- 4 mmHg, P < 0.05). Associated with the PEH was a reduction in TPR (from 28 +/- 3 to 19 +/- 2 mmHg/kHz; P < 0.05) and an elevation in CO (from 5.7 +/- 0.4 to 7.2 +/- 0.5 kHz; P < 0.05). The reductions in arterial pressure and TPR were associated with a decrease in LSNA (from 98 +/- 3 to 49 +/- 6%; P < 0.05). These results suggest that PEH is mediated by reductions in TPR and SNA.

Arterial baroreflex modulation of heat-induced vasodilation in the rabbit ear.

The purpose of this study was to determine whether nonthermal baroreflexes arising from cardiopulmonary and/or arterial baroreceptors modulate rabbit ear blood flow (EBF) during hyperthermia. Intact and sinoaortic-denervated (SAD) rabbits were chronically instrumented with a Doppler ultrasonic flow probe for measurement of EBF velocity (kHz). During whole body heating in conscious rabbits, EBF and ear vascular conductance (EVC) increased as core temperature increased until maximal plateau levels of EBF and EVC were reached. The maximal plateau level of EVC attained during heat stress was lower in SAD than in intact rabbits. Subsequent intrapericardial administration of procaine at maximal EBF blocked cardiac afferents but did not alter EVC in either animal group. In a second experiment, ramp decreases in mean arterial pressure were produced by vena caval occlusion at maximal EBF. In intact rabbits, EBF and EVC decreased linearly as mean arterial pressure fell, but EBF and EVC did not decrease during vena caval occlusion in SAD rabbits. Thus neither pharmacological nor mechanical unloading of cardiac baroreceptors results in reflex vasoconstriction in the heat-stressed rabbit ear. However, baroreflexes arising from arterial baroreceptors may modulate EBF in heat-stressed rabbits.

Cerebral blood flow in rabbits during the nasopharyngeal reflex elicited by inhalation of noxious vapor

We used chronically implanted Doppler ultrasonic flow probes to measure internal carotid and vertebral blood flow during the nasopharyngeal reflex elicited by inhalation of formaldehyde vapor in conscious rabbits. Internal carotid flow gradually increased to 157±5% of baseline and vertebral artery increased to 123±9% of baseline, with maximum values reached approximately 20–40 s after administration of vapor, at a time when arterial pO 2 had decreased from 80±3 to 53±4 mmHg. Increases in flow were associated with increases in vascular conductance. The delayed increases in cerebral blood flow contrasted with rapid decreases in ear and distal aortic flows, measured at the same time. Our results indicate that forebrain vascular conductance increases in response to inhalation of noxious vapor, possibly reflecting cerebrovascular events associated with hypoxemia.

Mural blood flow distribution in the large colon of horses during low-flow ischemia and reperfusion

SUMMARY Six horses were subjected to 3 hours of low-flow ischemia and 3 hours of reperfusion of the large colon. After induction of anesthesia, the large colon was exteriorized through a ventral midline celiotomy. Colonic blood flow was measured continuously, using Doppler ultrasonic flow probes placed on the colonic arteries supplying the dorsal and ventral colons and was allowed to stabilize for 15 to 30 minutes after instrumentation. Low-flow ischemia was induced by reducing colonic arterial blood flow to 20% of baseline (bl) flow. Colonic mucosal, seromuscular, and full-thickness blood flow were determined on a tissue-weight basis by injecting colored microspheres proximally into the colonic artery supplying the ventral colon. Reference blood samples were obtained at a known flow rate from the colonic artery and vein at a site more distal to the site of injection. Left ventral colon biopsy specimens were harvested at bl, 3 hours of ischemia, and 15 minutes of reperfusion. Blood and tissue samples were digested and filtered to collect the microspheres, and dimethylformamide was added to release the colored dyes. Dye concentration in blood and tissue samples was measured by use of spectrophotometry, and tissue-blood flow was calculated. Data were analyzed, using two-way anova for repeated measures; statistical significance was set at P &lt; 0.05. Doppler blood flow decreased to approximately 20% of BL, whereas microsphere blood flow ranged between 13.7 and 15.5% of bl at 3 hours of ischemia. Doppler-determined blood flow increased immediately on restoration of blood flow, reached 183% of bl at 15 minutes of reperfusion, and remained at or above bl throughout 3 hours of reperfusion. This reactive hyperemia was also detected, using the colored microspheres; blood flow increased to 242 and 327% of bl at 15 minutes of reperfusion in the mucosal and seromuscular layers, respectively. Mucosal blood flow was not different from seromuscular blood flow at any time, indicating relatively equal distribution of blood flow between these 2 layers. As determined from the venous reference samples, there was no evidence of arteriovenous anastomoses.

Acute exercise enhances nitric oxide modulation of vascular response to phenylephrine

The influence of the release of endothelium-derived nitric oxide (NO) on the vasoconstrictor response to phenylephrine (PE) was evaluated before and after a single bout of dynamic exercise. Each rat ran on a motor-driven treadmill at 12-18 m/min, 10-18% grade until exhaustion (avg time 45 min). Sprague-Dawley rats (n = 6) were instrumented with a Doppler ultrasonic flow probe around the right common iliac artery. Just distal to the flow probe, a catheter was placed into the right iliac artery for local infusions. A Teflon catheter was placed in the descending aorta to measure mean arterial blood pressure (MAP) and heart rate (HR). PE (0.005-0.075 microgram/kg) and NO inhibitor N omega-nitro-L-arginine methyl ester hydrochloride (L-NAME, 0.2-0.25 mg/kg) were injected into the functionally isolated hindlimb. HR and MAP were not altered by any of the injections because we selected doses below those which elicited systemic responses. Dose-response curves to PE were generated in the control and postexercise condition, with and without the NO synthase inhibitor L-NAME. Exercise significantly attenuated the maximal vasoconstrictor response to PE (45.6 +/- 1.6%). L-NAME enhanced the maximal vasoconstrictor response to PE 49.8 +/- 4.5% in the control condition and 121.4 +/- 5.9% in the postexercise conditions. Thus, although NO inhibition enhanced the vasoconstrictor response to PE in the control and postexercise conditions, the enhanced vasoconstrictor response to PE after L-NAME was significantly greater in the postexercise condition. Results suggest that NO contributes to the exercise induced attenuation of alpha 1-adrenergic receptor stimulation.

Cardiac afferents attenuate the muscle metaboreflex in the rat.

The influence of cardiac afferents on the muscle metaboreflex was examined in 16 rats instrumented with a Silastic-tipped catheter in the pericardial space and right atrium, Doppler ultrasonic flow probe and a pneumatic vascular occluder around the terminal aorta, and a Teflon catheter in the thoracic aorta. In protocol I (cardiac efferent and afferent blockade), the muscle metaboreflex was examined under three experimental conditions: 1) control, 2) cardiac autonomic efferent blockade [intrapericardial methylscopolamine (10 micrograms/kg) and propranolol (50 micrograms/kg)], and 3) combined cardiac autonomic efferent and afferent blockade (intrapericardial procainamide, 2%). In protocol II (blood volume expansion), the muscle metaboreflex was examined before and after 15% blood volume expansion. Mild treadmill exercise (9 m/min, 10% grade) increased heart rate (71 +/- 9.4 beats/min), mean arterial pressure (12 +/- 2.0 mmHg), and terminal aortic blood flow velocity (6 +/- 1.0 kHz). During exercise, a reduction of terminal aortic blood flow velocity (10.5 +/- 1.1%) reduced mixed venous PO2 18 +/- 6%. The gain of the muscle metaboreflex in the control condition was 14.6 +/- 2.9 mmHg/kHz. Efferent blockade reduced the gain 51 +/- 7%. However, combined cardiac efferent and afferent blockade increased the gain 207 +/- 64% above the efferent blocked condition and restored the gain to levels above those obtained in the control condition (18.3 +/- 4.6 mmHg/kHz). In addition, 15% blood volume expansion reduced the gain of the muscle metaboreflex regulation of mean arterial pressure and heart rate (44 +/- 9.5% and 41 +/- 12.0%, respectively). Thus cardiac afferents tonically inhibit the pressor response to a reduction in terminal aortic blood flow velocity during exercise.