Initial Rise In Blood Pressure Research Articles

Temporal changes in blood pressure following prehospital rapid sequence intubation

BackgroundRapid Sequence intubation (RSI) is an airway procedure that uses sedative and paralytic drugs to facilitate endotracheal intubation. It is known that RSI could impact blood pressure in the peri-intubation...

Early blood pressure response to isometric exercise is attenuated in obese individuals who have undergone bariatric surgery

ObjectiveBlood pressure (BP) reactivity to stress is predictive of the development of cardiovascular disease. Cardiovascular reactivity is attenuated in individuals after bariatric surgery; however, the underlying mechanisms are not completely understood. We hypothesized the BP response at the onset of isometric handgrip exercise would occur earlier and to a lesser degree in individuals who underwent bariatric surgery when compared to obese adults and the reliance on total peripheral resistance (TPR) would be attenuated.MethodsTwenty‐six individuals [7 non‐obese (28±3 yrs, 23±1 kg/m2), 11 obese (33±2 yrs, 39±1 kg/m2), 8 post‐bariatric surgery (35±2 yrs, 29±1 kg/m2)] completed isometric handgrip exercise (40% maximum voluntary contraction) to exhaustion. Heart rate (HR, ECG) and arterial BP (brachial catheter) were measured continuously. Stroke volume was estimated from the pressure waveform and cardiac output (CO) and TPR were calculated. Peak change, time to peak, and rate of rise in BP were assessed during the first 30‐s of exercise.ResultsCompared to non‐obese controls, obese adults exhibited a slower initial rise in BP (9.3± 3.9 vs 21.7±2.5 s) and higher peak BP change (Δ6.7±2.1 vs Δ11.9±2.1 mmHg) at the onset of isometric handgrip exercise (p<0.05). Peak BP and the rate of rise were not different between individuals who underwent bariatric surgery (14.0±4.1 s, Δ5.6±1.3 mmHg) and non‐obese controls (p>0.05). Non‐obese controls exhibited an exercise‐mediated increase in CO whereas obese adults increased TPR (p<0.05). The increases in CO and TPR were less apparent in individuals who underwent bariatric surgery (p>0.05). Low cardiac baroreflex sensitivity (BRS) and heart rate variability (HRV: SDNN, standard deviation of normal to normal R‐R intervals) at rest were related to smaller increases in CO (BRS: R=0.47, p<0.01; SDNN: R=0.57, p<0.01) and greater increases in TPR (BRS: R=−0.49, p=0.01; SDNN: R=−0.60, p<0.01) during exercise.ConclusionsIn contrast to obese adults, individuals who underwent bariatric surgery exhibit a rapid rise in BP at the onset of isometric handgrip exercise. This rapid increase in BP is associated with a fall in TPR and results in lower peak BP at the onset of isometric exercise. These data suggest bariatric surgery attenuates BP reactivity to physical stress via improvements in the time‐course of hemodynamic responses and reflex autonomic adjustments.Support or Funding InformationNIH HL130339, NIH HL083947, NIH DK82424, NIH UL1 RR024150, Mayo Clinic Department of Anesthesiology, Mayo Foundation for Medical Education and ResearchThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Transient Increases In Blood Pressure After Spontaneous Bursts Of Muscle Sympathetic Nerve Activity: Contributions Of Cardiac Output And Systemic Vascular Conductance

Previously, a latency of 5.5 seconds between the occurrence of a burst of muscle sympathetic nerve activity (MSNA) and the subsequent peak arterial blood pressure (BP) response was reported. Although this BP increase was thought to be primarily due to peripheral vasoconstriction, beat-to-beat vascular conductance measures were not made. Furthermore, a transient cardio-acceleration was observed following MSNA bursts. However, whether an increase in cardiac output contributes to the BP response is unknown. PURPOSE: To assess the beat-to-beat fluctuations in cardiac output (CO) and systemic vascular conductance (SVC) following a spontaneous burst of MSNA. METHODS: In 7 young men, BP (finger photoplethysmography), stroke volume (SV; Modelflow), heart rate (HR; ECG) and MSNA (microneurography) were continuously measured during 30 minutes of supine rest. Beat-to-beat fluctuations in BP, CO (HR × SV) and systemic vascular conductance (SVC; CO/MAP) were characterized for 15 cardiac cycles following each individual MSNA burst using signal averaging to identify the temporal pattern for each variable and a peak response was calculated. RESULTS: A significant rise in diastolic BP was observed following each burst of MSNA with a peak increase of 4.35 ± 0.5 mmHg (+6.6 ± 0.7%; p<0.05) occurring at a latency of 5.4 ± 0.2 s. Within the first 2 cardiac cycles following an MSNA burst, the immediate (1.7 ± 0.05 s) increase in BP was associated with a 0.49 ± 0.10 L (+10 ± 0.03%; p<0.05) increase in CO. SVC was also transiently increased with CO during this initial period but then subsequently decreased by -0.005 ml·min-1mmHg-1 (-8.1 ± 0.4%; p<0.05), reaching a maximum reduction around the time of the peak increase in BP. CONCLUSIONS: These preliminary findings indicate that spontaneous bursts of MSNA consistently produce elevations in BP that appear to be mediated by alterations in both CO and SVC. The initial rise in BP is associated with an increase in CO that transitions to peripheral vasoconstriction, noted by the significant fall in SVC at the time of the peak BP response. Thus, it appears that both central and peripheral adjustments contribute to the transient rise in BP following a spontaneous burst of MSNA.

Cardiorespiratory effects of intravenous N-methyl-D-aspartate challenge in anaesthetized rats.

1. Experiments were performed to determine the effects of systemic application of N-methyl-d-aspartate (NMDA) on respiratory variables and blood pressure in 22 urethane/chloralose-anaesthetized, spontaneously breathing rats. 2. Bolus injection of NMDA at a dose of 27 micro mol/kg, i.v., in neurally intact rats evoked a depression of breathing, most apparent at 30 s, comprising a decrease in tidal volume (P < 0.001) and respiratory rate (P < 0.001). The expiratory apnoea appeared in three intact rats only. 3. The respiratory effects of NMDA were independent of the vagal integrity between lungs and the nodose ganglia. Elimination of supranodose connection to the medulla reduced the prolongation of the expiratory time (P < 0.01). 4. N-Methyl-d-aspartate induced an initial rise in blood pressure followed by hypotension in rats treated by infra- and supranodose vagotomy. 5. It is concluded that the respiratory response to systemic NMDA challenge occurs beyond lung vagi and indicates that neurons of the nodose ganglia contribute to NMDA inhibition of the expiratory time.

Brain nitric oxide changes after controlled cortical impact injury in rats.

Nitric oxide (NO) and the NO end products, nitrate and nitrite, were measured at the impact site after a 5-m/s, 3-mm deformation controlled cortical impact injury in rats. Immediately after the impact injury and the NO and microdialysis probes could be replaced, there was an increase from baseline in NO concentration of 83 +/- 16 (SE) nM, compared with 0.5 +/- 4 nM in the sham injured animals (P < 0.001). This marked increase in NO occurred at the time of the initial rise in blood pressure (BP) and intracranial pressure (ICP) in response to the injury. After the initial increase in BP and ICP, the BP decreased and stabilized at a value which was approximately 20 mmHg below the preinjury values, and ICP plateaued at an average value of 20 mmHg, compared with 8 mmHg in the sham-injured animals. This provided an average cerebral perfusion pressure of 40-50 mmHg, compared with 65-75 mmHg for the sham-injured animals. These values were relatively constant for the remainder of the 3-h monitoring period. The NO values also stabilized during this time period. By 1 h after the impact injury the NO concentration measured directly using the NO electrode had decreased from baseline values by an average value of 25 +/- 6 nM. NO concentration remained significantly lower than baseline values throughout the remainder of the 3-h monitoring period. The concentration of nitrate/nitrite in the dialysate fluid also decreased by an average value of 341 +/- 283 nM 20-40 min after the injury. Dialysate nitrite/nitrate concentrations remained less than the preinjury baseline values throughout the remainder of the 3-h monitoring period. Preinjury treatment with L-nitro-arginine methyl ester (L-NAME) blunted the injury-induced increase in NO and resulted in more severe immediate intracranial hypertension and more severe systemic hypotension at one hour after injury. Mortality was also 67% with L-NAME pretreatment, compared with 1% in untreated animals.

Pressor responses to brain dopaminergic stimulation.

1. Systemic administration of a dopamine D2 receptor agonist, such as quinpirole, causes a centrally mediated rise in blood pressure (BP) with a maximum at 1-2 min after injection. At 30 min after injection, when BP has returned to baseline, further treatment with these drugs has little effect on BP. Moreover, the antihypertensive effects of sympathoinhibitory drugs, such as clonidine and rilmenidine, is markedly inhibited. Increased circulating levels of vasopressin contribute to the initial rise in BP, but return to baseline thereafter. Differential changes in sympathetic vasomotor tone may be involved in the apparent desensitization induced by quinpirole. 2. Stimulation of the region of origin of the mesolimbic dopamine (DA) system in the brain, the ventral tegmental area, causes a long-lasting increase in BP. In this model, circulating levels of vasopressin are moderately increased through a non-dopaminergic mechanism. Dopaminergic stimulation causes a functional potentiation of the effect of vasopressin, resulting in an increase in BP. 3. Spontaneously hypertensive rats (SHR) display several changes in central dopaminergic responses. Dopamine levels in the brain are normal, while resting DA activity appears reduced. Partial depletion of forebrain DA levels, particularly in the nigrostriatal system, causes an inhibition of the development of hypertension and normalizes deficient functional responses to dopaminergic drugs in the SHR. 4. These results show that brain DA is involved in several aspects of cardiovascular regulation and may be involved in the development of hypertension. The widespread involvement of brain DA systems in behavioural, hormonal and cardiovascular mechanisms suggests that these systems play an important role in the integration of stress and environmental stimuli with homeostatic mechanisms in the body.

Endogenous nitric oxide buffers blood pressure variability between 0.2 and 0.6 Hz in the conscious rat.

Shear stress is a potent stimulus for the formation and release of nitric oxide (NO). It seems, therefore, possible that a short-term increase in arterial blood pressure (ABP), which leads to a concomitant rise in endothelial shear stress, enhances NO release. The latter elicits a relaxation of vascular smooth muscle cells that, in turn, counteracts the initial rise in blood pressure (BP). Thus this chain of events may constitute a negative feedback loop reducing BP variability (BPV). To test this hypothesis, BP-time series were determined via telemetry in freely moving conscious Sprague-Dawley rats. Because it was reported recently that NO effects on ABP are more pronounced in females, the experiments were performed on 2 groups consisting of 10 female and 11 male animals. This was done under control conditions and after fixing NO plasma levels via an intravenous bolus of 15 mg/kg body wt N(G)-nitro-L-arginine methyl ester together with a continuous infusion of nitroprusside (15 +/- 0.8 microg/min). This combined infusion maintained mean ABP and heart rate at physiological levels, thus avoiding as much as possible interferences with other reflexes, e.g., the baroreflex. To quantitate BPV, fast Fourier transforms of the BP-time series were determined. The absolute power in the frequency range below 1 Hz increased during fixed NO to approximately 350% vs. control animals (female control, 2.1 x 10(9) +/- 1.5 x 10(8) mmHg2 vs. fixed NO, 8.0 x 10(9) +/- 1.3 x 10(9) mmHg2, P < 0.005; male control, 3.4 x 10(9) +/- 4.6 x 10(8) mmHg2 vs. fixed NO, 8.3 x 10(9) +/- 2.0 x 10(9) mmHg2, P < 0.05). This was mainly caused by a substantial rise in the power ranging from 0.2 to 0.6 Hz, which increased roughly fourfold in both females and males. It is concluded that the NO system is a potent buffer of spontaneous BP oscillations in the freely moving rat. This system is most efficient in buffering frequencies within the range of 0.2-0.6 Hz and shows no gender-specific differences with respect to its BP buffering capacity.

The Effect of Caffeine on Daytime Ambulatory Blood Pressure

Caffeine produces an acute increase in blood pressure in the research laboratory, but its effect on the ambulatory blood pressure during normal daily activities is unknown. In 25 normotensive, caffeine-naive subjects, daily administration of 400 mg caffeine produced a small increase (+3/+3 mm Hg, P less than .001) in ambulatory daytime blood pressure on the first day, with values returning to baseline by the third day. The initial rise in blood pressure was associated with a fall in heart rate (-3 beats/min, P less than .02). Readings taken the morning following the first day of caffeine ingestion did not show any persistent effect of caffeine on blood pressure. A 400 mg dose of caffeine causes a small increase in daytime ambulatory blood pressure, but tolerance develops with daily caffeine consumption. Infrequent ingestion of caffeine may cause a transient rise in blood pressure which is unlikely to be harmful to an individual but might influence the diagnosis of hypertension in a patient with a borderline elevated blood pressure.

The significance of abnormal systolic blood pressure response during supine ergometer exercise and postexercise in ischemic heart disease, studied by exercise radionuclide ventriculography.

The prognostic value of abnormal postexercise systolic blood pressure (BP) response has not been investigated. Therefore, the significance of abnormal BP response during exercise and postexercise was examined in 169 patients with ischemic heart disease subjected to supine ergometer exercise gated equilibrium radionuclide ventriculography, coronary arteriography, and follow up averaging 3.6 years. Abnormal BP response during exercise (exertional "hypotension") was defined as 1) a failure of BP to rise by at least 11 mmHg or 2) an initial rise in BP but subsequent fall by more than 10 mmHg during exercise. Abnormal BP response during postexercise (postexercise "hypertension") was defined as an increase of more than 10 mmHg above the peak exercise BP. Of 169 patients, 51 (30%) had an abnormal BP response. Four types of BP response were identified: exertional "hypotension" (group 1a, n = 11), postexercise "hypertension" (group 1b, n = 30), exertional "hypotension" with postexercise "hypertension" (group 1c, n = 10) and normal BP response (group 2, n = 118). Both average exercise duration and peak heart rate were significantly lower in groups 1a, 1b and 1c than in group 2. The severity of exercise ST-segment depression was greater in groups 1b and 1c than in group 2. However, there was no significant difference in the severity of exercise ST-segment depression between group 1a and group 2. A decline in ejection fraction occurred more frequently in groups 1b and 1c than in group 2. Patients in groups 1a, 1b and 1c had more extensive coronary artery disease (CAD) than did patients in group 2. Medically treated patients with an abnormal BP response (groups 1a, 1b and 1c) had a poorer prognosis than did those with a normal BP response (group 2). These findings suggest that an abnormal BP response during supine exercise is infrequent, but is usually associated with impaired exercise tolerance and severe CAD. An abnormal postexercise BP response is also infrequent, but is more closely associated with evidence of myocardial ischemia and global left ventricular dysfunction than exertional "hypotension". In conclusion, postexercise "hypertension" has the same value as exertional "hypotension" as a predictor of poor prognosis.

Infusions of chemicals into the brain and the development of sustained elevations of blood pressure in the rat

Osmotic minipumps were used to infuse carbachol chloride (1.23 μg/hr), echothiophate iodide (0.5 μg/hr), histamine dihydrochloride (10 μg/hr), prostaglandin E 2 (1.0 μg/hr) and thyrotropin-releasing hormone (0.5 and 5.0 μg/hr) solutions into the cerebral ventricles of unanesthetized rats and blood pressure was measured by the tail-cuff method. Histamine dihydrochloride, prostaglandin E 2 and thyrotropin-releasing hormone produced an initial rise in blood pressure, but were not effective in producing sustained elevations in blood pressure. Carbachol infusions elevated blood pressure throughout the 7-day infusion period when results were compared to saline-infused animals. Infusions of echothiophate iodide, an anticholinesterase agent, produced an initial rise in blood pressure but these pressor effects were not sustained. In animals infused with echothiophate for 7 days, the pressor response to a challenge dose of echothiophate was diminished.

Electroencephalographic studies of stunning and slaughter of sheep and calves: Part 1—The onset of permanent insensibility in sheep during slaughter

The time of onset of permanent insensibility, subsequent to incision of the major blood vessels of the neck, was studied in sixteen adult sheep and five one-week-old lambs. Insensibility was determined from the study of electroencephalograms (EEG) and interpretation was based on the amplitude and pattern of fast wave signals of a transhemispheric bipolar derivation. In both adult sheep and lambs, conscious at the time of slaughter, insensibility occurred within 2 to 7 s and EEG traces became isoelectric between 10 and 43 s. In sheep which were lightly anaesthetised at the time of slaughter, EEG traces became isoelectric between 18 and 70 s after incision of the major blood vessels of the neck. In one sheep which was slaughtered by severance of the carotid artery and jugular vein on one side of the neck only, the onset of insensibility was delayed for 29 s. In the majority of animals, the electrocardiogram (ECG) continued to show a normal pattern for more than 10 min after slaughter. There was an initial rise in blood pressure in the first 5 to 7 s and it remained elevated for a further 10 to 20 s. The results of this work are discussed with reference to definition of death appropriate for statutory purposes and the implications for the humane slaughter of sheep.

Regional pre- and postganglionic sympathetic activity during experimental paraoxon poisoning.

The effects of 0.4 or 0.8 mg paraoxon/kg i.v. on circulation and regional pre- and postganglionic sympathetic activity were studied in anaesthetized rabbits. At both doses, the discharges of the preganglionic efferents increased slowly, whereas the changes in activity of postganglionic efferents differed. Concomitantly with a transient initial rise in blood pressure a temporary increase of discharges to the skeletal muscles and to the intestine was observed which is attributed to spontaneous firing of the regional ganglionic cells. After injection of 0.4 mg/kg there occasionally occurred a second pressor reaction conditioned by enhancement of preganglionic activity and facilitated transmission in certain sympathetic ganglia. After injection of the higher dose, postganglionic activity generally decreased except for the discharges of gastrointestinal efferents, which increased. Arterial blood pressure, cardiac output and total peripheral resistance fell markedly. A shock syndrome occurred which could be controlled by atropine injection if timely. From the results it was concluded that the higher dose of paraoxon blocked synaptic transmission in the paravertebral ganglia of the sympathetic trunk, and facilitated impulse transmission in the prevertebral abdominal ganglia.

Synthesis of angiotensin II antagonists containing N- and O-methylated and other amino acid residues.

[1-N-Methylisoasparagine,8-isoleucine]- (I), [1-sarcosine,4-N-methyltyrosine,8-isoleucine]- (II), [1-sarcosine,5-N-methylisoleucine,8-isoleucine]- (III), [1-sarcosine,8-N-methylisoleucine]- (IV), [1-sarcosine8k-N-methylisoleucine,8-N-methylisoleucine]- (V), [1-sarcosine,8-O-methylthreonine]- (VI), [1-sarcosine,8-methionine]- (VII), and [1-sarcosine,8-serine]angiotensin II (VIII), synthesized by Merrifield's solid-phase procedure, possess respectively 0.8, 0.3, 0.5, 1.0, 0.0, 0.5, 3.7, and 0.7% pressor activity of angiotensin II (vagotomized, ganglion-blocked rats). They caused an initial rise in blood pressure (30 min of infusion, 250 ng/kg/min in vagotomized, ganglion-blocked rats) of 16.57, 9.80, 22.80, 32.00, 7.00, 15.06, 32.50, and 11.42 mmHg and showed secretory activity (isolated cat adrenal medulla) of 1.0, 0.1, 0.01, 0.1, less than 0.01, 0.1, less than 0.01, and 0.05% of angiotensin II. On isolated organs pA2 values (rabbit aortic strips) of 8.74, 7.44, 7.64, 7.85, 7.89, 8.76, 8.63, and 8.08, and pA2 values (cat adrenal medulla of 8.16, 9.16, 9.31, 8.00, 8.00, 7.00, 9.16, and 9.33 were obtained. Dose ratios (ratio of ED20 of angiotensin II during infusion of the antagonist and before infusion of the antagonist) in vagotomized, ganglion-blocked rats, infused at 250 ng/kg/min, were 33.43, 2.14, 3.26, 2.99, 0.62, 62.52, incalculable, and 11.15, respectively. The results obtained suggest that (a) analogs I and VI are potent antagonists of the pressor response of angiotensin II in normal rat, VI being the most potent antagonist thus far synthesized; (b) replacement of position 4 (Tyr) with MeTyr or position 5 and/or 8 (Ile) with Melle in [1-sarcosine,8-isoleucine]angiotensin II reduced the antagonist activity of this peptide (rabbit aortic strips and rats), indicating that steric hindrance imposed due to N-methylation in positions 4, 5, or 8 was not favorable in eliminating the initial pressor activity or prolonging the duration of action of [Sar1, Ile8]angiotensin II without reducing its antagonistic properties; (c) except II, none of the analogs showed any enhanced duration of action, suggesting that N-methylation in positions 5 or 8 did not afford protection against proteolytic enzymes; and (d) perfusion studies in cat adrenals indicated that all of these analogs are only very weak secretagogues. With the exception of [Sar1,Thr(ObetaMe)8]angiotensin II, which gave lower antagonistic properties, all other analogs had either similar antagonistic properties or were better antagonists in adrenal medulla than in smooth muscle.

Pharmacodynamic Actions of (S)-2-[4,5-Dihydro5-Propyl-2 (3H)-Furylidene]-1, 3-Cyclopentanedione (Oudenone)

The pharmacodynamic actions of (S)-2-[4,5-dihydro-5-propyl-2(3H)-furylidene]-l,3-cyclopentanedione (oudenone) were studied in both anesthetized animals and isolated organs. Oudenone (10-40 mg/kg i.v.) induced an initial rise in blood pressure followed by a prolonged hypotension in the anesthetized rats. In unanesthetized spontaneously hypertensive rats (SHR), oudenone (5–200 mg/kg p.o.) caused a doserelated decrease in the systolic blood pressure. The initial pressor effect was diminished by pretreatments with phentolamine, guanethidine, hexamethonium and was abolished in the pithed rats. In addition, intracisternal administrations of oudenone (100–600 μg/kg) showed a marked increase in blood pressure in the anesthetized rats, suggesting that the pressor effect may be due to centrally mediated actions. Oudenone, given intra-arterially into the femoral artery (400–800 μg/kg), caused a long-lasting vasodilation in anesthetized dogs. At a relatively high dose (40 mg/kg i.v.), oudenone antagonized all pressor responses to autonomic agents and central vagus nerve stimulation in anesthetized rats and dogs, however, oudenone showed no anti-cholinergic, -histaminergic, beta-adrenergic and adrenergic neuron blocking properties.

Pharmacodynamic actions of (S)-2-[4,5-dihydro-5-propyl-2-(3H)-furylidene]-1,3-cyclopentanedione (oudenone).

The pharmacodynamic actions of (S)-2-[4,5-dihydro-5-propyl-2(3H)-furylidene]-1,3-cyclopentanedione (oudenone) were studied in both anesthetized animals and isolated organs. Oudenone (10--40 mg/kg i.v.) induced an initial rise in blood pressure followed by a prolonged hypotension in the anesthetized rats. In unanesthetized spontaneously hypertensive rats (SHR), oudenone (5--200 mg/kg p.o.) caused a dose-related decrease in the systolic blood pressure. The initial pressor effect was diminished by pretreatments with phentolamine, guanethidine, hexamethonium and was abolished in the pithed rats. In addition, intracisternal administrations of oudenone (100--600 mug/kg) showed a marked increase in blood pressure in the anesthetized rats, suggesting that the pressor effect may be due to centrally mediated actions. Oudenone, given intra-arterially into the femoral artery (400--800 mug/kg), caused a long-lasting vasodilation in anesthetized dogs. At a relatively high dose (40 mg/kg i.v.), oudenone antagonized all pressor responses to autonomic agents and central vagus nerve stimulation in anesthetized rats and dogs, however, oudenone showed no anti-cholinergic,-histaminergic, beta-adrenergic and adrenergic neuron blocking properties.

Respiratory responses to chemical pulses in the cerebrospinal fluid of cats.

1. In cats anaesthetized with pentobarbitone, the fluid spaces in and around the brain stem were perfused from the third ventricle to the foramen magnum with artificial cerebrospinal fluid (c.s.f.) flowing usually at the rate of 5 ml/minute. Test solutions were substituted for the artificial c.s.f. without switching artifact for periods varying from 5 to 60 seconds. Observations were made on respiratory excursions, end-expiratory% CO(2) and arterial blood pressure.2. Perfusion with sucrose solution equiosmolar with the c.s.f. produced no respiratory or cardiovascular response. Replacement of sodium with potassium (60 to 133 mM) resulted in a prompt but mild respiratory stimulation and a delayed fall in blood pressure associated with a slowing of the heart beat. Replacement of sodium with magnesium (40 to 131 mM) resulted in a late prolonged apneustic depression of breathing and in an early but slight reduction in blood pressure.3. Procaine (1 to 50 mg/ml) elicited a respiratory response similar to that of excess magnesium; however, an initial rise in blood pressure to as high as 200 mmHg was evoked with procaine. Nicotine (0.05 to 0.5 mg/ml) produced an immediate brief bradypnea followed by a vigorous and slowly reversing hyperpnea accompanied most often by a fall in blood pressure. Tachyphylaxis was observed in the response to nicotine. Noradrenaline (0.001 and 0.1 mg/ml) did not produce any effect, and it did not alter the responses elicited by procaine and nicotine given by perfusion either simultaneous with or subsequent to the noradrenaline. Acetylcholine (0.5 mg/ml) produced weak transient respiratory stimulation and a small fluctuation in blood pressure which disappeared in repeated tests. Methacholine (1 mg/ml) caused a brief hyperpnea and a fall in blood pressure both of which were abolished after atropine (0.2 mg) was injected into the third ventricle. Pilocarpine (10 mg/ml) elicited no change in respiration or blood pressure. Respiratory and cardiovascular effects produced by strychnine (1 mg/ml) were attributable non-specifically to convulsive movements of the animal. Ethamivan (1 mg/ml) produced a single deep breath and a slowly reversing rise in blood pressure. Cyanide (0.5 mg/ml) barely stimulated the respiration but it produced a long lasting rise in blood pressure. Ethyl alcohol (0.1 ml/ml) elicited brisk though brief respiratory stimulation and a short lasting fall in blood pressure.4. It was shown that the effects of procaine and nicotine were not qualitatively altered when the perfusion effluent was collected through a ventral craniotomy instead of the cisterna magna.

Cardiovascular reflex responses to cutaneous and visceral stimuli in spinal man.

1. A study has been made of the effects of pinprick and a cold pack applied to the skin above and below the level of denervation, deep inspiration, squeezing the chest, and bladder percussion in non-bedridden patients with chronic, closed, complete, localized transection of the cervical spinal cord. Variables studied were blood pressure, heart rate, calf blood flow, hand blood flow and occluded vein pressure in the hand and foot.2. Cutaneous stimuli above the lesion, mental arithmetic and noise from gunshot produced no response.3. Pinprick and cold applied below the lesion usually produced an increase in mean arterial pressure, little change in pulse pressure or heart rate, clear decreases in calf and hand blood flow, and occasional venoconstriction.4. Deep inspiration produced an initial rise in blood pressure and heart rate which was sometimes followed by a decrease in one or both. Squeezing the chest usually produced an increase in blood pressure and a decrease in heart rate. Both stimuli caused decreases in calf and hand blood flow and venoconstriction, the latter being more common after squeezing the chest.5. Bladder percussion produced contraction of the wall of the bladder and this was regularly associated with increased arterial mean and pulse pressures, a decreased heart rate and calf and hand blood flow, and venoconstriction. The responses occurred whether or not the bladder was full and whether or not a rise of intravesical pressure occurred.

Modification of the cardiovascular effects of L-dopa in anesthetized dogs by inhibitors of enzymes involved in catecholamine metabolism.

The influence of various enzyme inhibitors on the cardiovascular effects of L -dopa (methylester) has been studied to determine the sites of action of the drug or a responsible metabolite. L -Dopa, 10 mg/kg, iv, had minor early effects on heart rate and blood pressure in normal dogs, but in animals with inhibition of monoamine oxidase (MAO), it caused tachycardia and severe hypotension of gradual onset. When MAO was inhibited, earlier doses of a dopamine β-oxidase inhibitor (FLA 63) did not significantly modify the effects of L -dopa; prior administration of a decarboxylase inhibitor, NSD 1055 or Ro 4-4602, prevented all but the initial effects; selective extracerebral decarboxylase inhibition with MK 486 ( L -α-hydrazino-α-methyldopa) prevented the tachycardia but not the hypotension. DL - threo -Dihydroxyphenylserine caused an initial rise in blood pressure in dogs with MAO inhibition, had less pressor activity when peripheral decarboxylase was also inhibited, and in both cases did not cause the hypotension characteristic of L -dopa. L -Dopa enhanced pressor responses and especially associated bradycardic responses to norepinephrine in dogs with MAO inhibition. This action was prevented by all decarboxylase inhibitors but not FLA 63. Responses to angiotensin were similarly augmented. Thus, MAO inhibition enabled L -dopa to induce severe hypotension, which appeared to rely on a central conversion to dopamine; the other effects were probably mediated by peripherally formed dopamine.

THE EFFECT OF ALCURONIUM AND TUBOCURARINE ON BLOOD PRESSURE AND HEART RATE: A CLINICAL COMPARISON

SUMMARY The effects of alcuronium (0.15 and 0.3 mg/kg) and tubocurarine (0.3 and 0.6 mg/kg) on arterial pressure and heart rate and rhythm have been compared in forty patients during nitrous oxide, oxygen and pethidine anaesthesia and in twenty patients during nitrous oxide, oxygen and halothane anaesthesia, prior to surgery. When halothane was used only the smaller doses of relaxants were given. Patients were divided into six homologous groups of ten patients. Both relaxants caused a fall in arterial pressure which was more pronounced during halothane anaesthesia. The fall in pressure was equal in degree after both relaxants but the period of maximum lowering was different, being 3–5 minutes after alcronium and 10–15 minutes after tubocurarine. This difference might be explained by the tubocurarine-induced initial rise in blood pressure which was probably due to pain from venous irritation. Alcuronium had a slight tachycardic effect which was more pronounced during halothance anaesthesia. No e.c.g. changes were seen.

Mechanisms of the pressor and depressor actions of St 155 (2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride, catapres ®)

St 155 (Catapres ®) has recently been found effective in the treatment of hypertension. The mechanism of its antihypertensive action has been investigated in animal experiments. These indicate that it differs from other clinically useful antihypertensives in its mode of action. In the cat, intravenous injections of St 155 produced an initial rise in blood pressure and a contraction of the nictitating membranes. After treatment with cocaine the pressor response was unchanged, and the contraction of the nictitating membrane was not reduced after denervation of the membrane. These sympathomimetic effects of St 155 are therefore not due to the release of endogenous catecholamines. Since these effects were blocked by phentolamine, they appear to be due to an action on the α-adrenoreceptors. Following the initial pressor response, St 155 produced a long lasting reduction of the blood pressure. St 155 had no ganglion blocking or adrenergic neurone blocking activity and did not block α- or β-adrenoreceptors; the depressor response was therefore not due to impairment of peripheral sympathetic function. The fall in blood pressure was unaffected by pretreatment with atropine or by propranolol, and was therefore not due to effects on muscarinic receptors or β-adrenoreceptors. However there was no fall in blood pressure in spinal cats or in cats treated with guanethidine. It is suggested that the depressor action of St 155 may therefore be due to a central reduction of sympathetic outflow to the heart and blood vessels.