Moderate Hypotension Research Articles

Association Between Hemodynamic Parameters and the Degeneration of Sustained Ventricular Tachycardias into Ventricular Fibrillation in Rats

Sustained ventricular tachycardias (VT) often degenerate into ventricular fibrillation (VF). In the present study, the impact of VT on mean arterial blood pressure (MAP), myocardial blood flow (MBF), and myocardial oxygen consumption (MVO2) was assessed. In addition, the degeneration of sustained VT into VF was analysed with respect to MAP. MBF was measured in 48 anesthetized rats with colored microspheres; arterial catecholamine levels were measured by HPLC in 16 additional rats during control conditions and VT. MBF (4.66±1.29 ml/g/min; mean±s.d.) did not change with the onset of VT (5.37±1.92 ml/g/min,n.s.). Epinephrine (0.22±0.13 ng/ml) and norepinephrine (0.37±0.12 ng/ml) increased during VT (3.55±2.68 ng/ml,P<0.01; 0.88±0.44 ng/ml,P<0.05), respectively. VF was more frequent when MAP remained normal (MAP>80 mmHg: 26%) than with hypotension (MAP<80 mmHg: 2%,P<0.05). Mechanical failure was observed in 10% of rats with severe hypotension (MAP<60 mmHg), and 2% with moderate hypotension (MAP 60–80 mmHg). The endo-epicardial MBF ratio in the VF group was significantly lower than that in the non-VF group (0.94±0.17v1.11±0.24,P<0.05). Conclusions: severe hypotension predisposes to the occurrence of acute mechanical failure during VT; moderate hypotension during VT, however, serves as a protective mechanism against VF in structurally normal hearts. Subendocardial hypoperfusion in the presence of an increased energy demand during VT is suggested to be responsible for the initiation of VF.

Cardiovascular effects of central choline during endotoxin shock in the rat.

The cardiovascular effects of intracerebroventricular (i.c.v.) administration of choline were studied in endotoxin-treated rats. Intravenous (i.v.) endotoxin (20 mg/kg) caused a moderate hypotension and tachycardia within 10 min of treatment. Choline (50, 100, and 150 microg; i.c.v.) increased blood pressure and decreased heart rate in this condition in a dose-dependent manner. Mecamylamine (50 microg; i.c.v.) pretreatment prevented the pressor and bradycardic responses to choline, whereas atropine (10 microg; i.c.v.) failed to alter both responses. Atropine pretreatment, alone, inhibited endotoxin-induced hypotension. The pressor responses to choline in endotoxin-treated rats were attenuated by pretreatment with hemicholinium-3 (20 microg; i.c.v.), a high-affinity neuronal choline-uptake inhibitor. Plasma vasopressin levels of endotoxin-treated rats were severalfold higher than those of control animals, and choline (50-150 microg; i.c.v.) produced further increases in plasma vasopressin in this condition. Mecamylamine abolished vasopressin response to endotoxin as well as to choline. The vasopressin receptor antagonist, (beta-mercapto-beta,beta-cyclopentamethylene-propionyl(1)-O-Me-Tyr2,Arg8 )-vasopressin (10 microg/kg; i.v.) administered 5 min after choline decreased blood pressure from the increased level to the precholine levels but did not alter bradycardia. These results indicate that, in rats treated with endotoxin, choline increases blood pressure and decreases heart rate by a presynaptic mechanism leading to the activation of central nicotinic cholinergic pathways. An increase in plasma vasopressin levels seems to be involved in the pressor, but not in the bradycardic response, to choline.

Cardiovascular Effects of Ethanol in Rats Selectively Bred for High or Low Sensitivity to the Hypnotic Effects of Ethanol

The cardiovascular effects of acute ethanol administration were studied in rats selectively bred for high (HAS) or low sensitivity (LAS) to the acute hypnotic effect of ethanol. In chronically cannulated, conscious animals, the intravenous administration of 1 g/kg of ethanol caused moderate hypotension and tachycardia in both HAS and LAS rats. The phenylephrine-induced reflex bradycardia and the baroreflex slope were significantly reduced by ethanol only in HAS and not in LAS rats. In urethane-anesthetized HAS rats, the baroreflex inhibitory action of ethanol was present under control conditions, but it was absent after depletion of endogenous GABA by treatment of the rats with 100 mg/kg of 3-mercaptopropionate. These findings confirm the role of endogenous GABA in the baroreflex inhibitory action of ethanol, and are compatible with the documented differential sensitivity of the GABAA, receptor complex to ethanol in HAS and LAS rats.

Modeling arterial hypotension during hemodialysis.

A mathematical model of the hemodynamic response to hemodialysis is presented. This model includes the dynamics of sodium, urea, and potassium in the intracellular and extracellular pools; fluid balance equations for the intracellular, interstitial, and plasma volumes; systemic and pulmonary hemodynamics; and the action of several short-term arterial pressure control mechanisms. The control mechanisms are triggered by information coming from both arterial and cardiopulmonary pressoreceptors, and they work on systemic arterial resistance, heart rate, and systemic venous unstressed volume. Moreover, the model hypothesizes that decreasing left atrial pressure below a given threshold causes a paradoxical withdrawal of the sympathetic drive and a consequent vasodepressor syncope. The model is used to simulate the pattern of the main hemodynamic quantities (systemic arterial pressure, heart rate, total systemic resistance, and cardiac output) during hemodialysis in several groups of patients (both hypotension resistant and hypotension prone) whose data were drawn from the clinical literature. The simulation results point out that the model is able to reproduce a variety of different conditions, including no hypotension, moderate hypotension, and severe hypotension with ultimate vasodepressor syncope, by adjusting a few parameters with clear physiological meanings. Hypotension is principally imputed to a loss of the sympathetic mechanisms working on systemic resistance and to an impairment of vascular refilling at the capillary wall. The results suggest that hypotension during hemodialysis is a complex phenomenon that depends on the superimposition of several concomitant factors working together that can lead to a variety of distinct individual patterns.

Adverse event with first-dose perindopril in congestive heart failure

The first-dose effect of perindopril, a long-acting angiotensin-converting-enzyme inhibitor (ACEI), has been reported to influence blood pressure (BP) to the same extent as placebo. Therefore, perindopril has been suggested as the drug of choice when initiating ACEI therapy in heart failure. I report a patient with a serious complication after the first dose of perindopril. A 61-year-old man with episodes of mild chest pain for 3 weeks was admitted with increasing dyspnoea. He had lung rales, raised jugular venous pressure, no heart or carotid murmurs, and no liver enlargement or peripheral oedema. On admission he was treated with intravenous diuretics and a low-dose dopamine infusion. The BP was never lower than 130/90 mm Hg and dopamine was stopped the following morning. Creatine kinase MB fraction rose to 70 IU (normal <12 IU) and electrocardiograms indicated an inferior myocardial infarction. Echocardiography revealed inferolateral left ventricular dyskinesia. Previously, he had been treated with antihypertensive drugs for 5 years. 4 months before admission he took captopril (unknown dosage), which was stopped after 1 month due to a skin rash. During hospital admission his BP remained stable at 130–150/80–90 mm Hg measured three times daily and he was in constant sinus rhythm. ACEI therapy was initiated with a single dose of 2 mg perindopril 5 days after admission. The evening BP was 130/80 mm Hg 5–6 h after perindopril. The next morning he had visual disturbances. The BP that had been 90/60 mm Hg before the patient expressed any complaints normalised spontaneously. Neurological examination revealed left-sided hemianopia and no other neurological disturbances. Computed tomography showed an ischaemic infarct of the region supplied by the right posterior cerebral artery. Laboratory values before start of perindopril were: sodium 137 mmol/L, potassium 3·8 mmol/L, and creatinine 138 mol/L. The patient was on oral furosemide 40 mg four times daily, spironolactone 25 mg daily, potassium supplement, aspirin 150 mg daily, and phenoxymethylpenicillin 800 mg three times daily (pneumonia was initially suspected but not verified and the patient was afebrile when perindopril was given). The visual defect remained the same at his discharge 9 days later. Severe and moderate hypotension after initiation of 2·5 mg enalapril occurred in 0·5% and 4·7%, respectively, of 1210 heart failure patients. In the studies of left ventricular dysfunction (7487 eligible patients), 0·04% developed a stroke and 2·2% became hypotensive when enalapril 2·5 mg twice daily was initiated with most patients on diuretics. Although withdrawal of diuretics has been recommended before initiation of ACEI, such action does not always prevent severe hypotension. Perindopril has a long half-life Sunscreen alone with SPF after 15 min

A simple mathematical model of the interaction between intracranial pressure and cerebral hemodynamics.

A simple mathematical model of intracranial pressure (ICP) dynamics oriented to clinical practice is presented. It includes the hemodynamics of the arterial-arteriolar cerebrovascular bed, cerebrospinal fluid (CSF) production and reabsorption processes, the nonlinear pressure-volume relationship of the craniospinal compartment, and a Starling resistor mechanism for the cerebral veins. Moreover, arterioles are controlled by cerebral autoregulation mechanisms, which are simulated by means of a time constant and a sigmoidal static characteristic. The model is used to simulate interactions between ICP, cerebral blood volume, and autoregulation. Three different related phenomena are analyzed: the generation of plateau waves, the effect of acute arterial hypotension on ICP, and the role of cerebral hemodynamics during pressure-volume index (PVI) tests. Simulation results suggest the following: 1) ICP dynamics may become unstable in patients with elevated CSF outflow resistance and decreased intracranial compliance, provided cerebral autoregulation is efficient. Instability manifests itself with the occurrence of self-sustained plateau waves. 2) Moderate acute arterial hypotension may have completely different effects on ICP, depending on the value of model parameters. If physiological compensatory mechanisms (CSF circulation and intracranial storage capacity) are efficient, acute hypotension has only negligible effects on ICP and cerebral blood flow (CBF). If these compensatory mechanisms are poor, even modest hypotension may induce a large transient increase in ICP and a significant transient reduction in CBF, with risks of secondary brain damage. 3) The ICP response to a bolus injection (PVI test) is sharply affected, via cerebral blood volume changes, by cerebral hemodynamics and autoregulation. We suggest that PVI tests may be used to extract information not only on intracranial compliance and CSF circulation, but also on the status of mechanisms controlling CBF.

Effects of Sinoaortic Denervation on Fos Expression in the Brain Evoked by Hypertension and Hypotension in Conscious Rabbits

We have previously shown [Li and Dampney (1994) Neuroscience 61, 613–634] that periods of sustained hypertension and hypotension each induces a distinctive and reproducible pattern of neuronal expression of Fos (a marker of neuronal activation) in specific regions of the brainstem and forebrain of conscious rabbits. The aim of this study was to determine the contribution of afferent inputs from arterial baroreceptors to the activation of neurons in these various brain regions that is caused by a sustained change in arterial pressure. Experiments were carried out on rabbits in which the carotid sinus and aortic depressor nerves were cut in a preliminary operation. Following a recovery period of seven to 10 days, a moderate hypertension or hypotension (increase or decrease in arterial pressure of 20–30 mmHg) was induced in conscious barodenervated rabbits for 60 min by the continuous infusion of phenylephrine or sodium nitroprusside, respectively. In control experiments, barodenervated rabbits were subjected to the identical procedures except that they were infused with the vehicle solution alone. Compared with the effects seen in barointact rabbits, [Li and Dampney (1994) Neuroscience 61, 613–634] the number of neurons that expressed Fos in response to hypertension was reduced by approximately 90% in the nucleus of the solitary tract and in the caudal and intermediate parts of the ventrolateral medulla. In supramedullary regions, baroreceptor denervation resulted in a reduction of approximately 60% in hypertension-induced Fos expression in the central nucleus of the amygdala and in the bed nucleus of the stria terminalis, but no significant reduction in the parabrachial complex in the pons. Following hypotension, the number of neurons that expressed Fos in barodenervated rabbits, compared with barointact rabbits, [Li and Dampney (1994) Neuroscience 61, 613–634] was reduced by approximately 90% in the nucleus of the solitary tract, area postrema, and caudal, intermediate and rostral parts of the ventrolateral medulla. Baroreceptor denervation also resulted in a similar large reduction in hypotension-induced Fos expression in many supramedullary regions (locus coeruleus, midbrain periaqueductal grey, hypothalamic paraventricular nucleus, and in the central nucleus of the amygdala and the bed nucleus of the stria terminalis in the basal forebrain). In the supraoptic nucleus, hypotension-induced Fos expression in barodenervated rabbits was reduced by 75% compared to barointact animals, but was still significantly greater than in control animals. There was also a high level of Fos expression, much greater than in control animals, in the circumventricular organs surrounding the third ventricle (subfornical organ and organum vasculosum lamina terminalis). The results indicate that in conscious rabbits the activation of neurons that occurs in several discrete regions at all levels of the brain following a sustained change in arterial pressure is largely dependent upon inputs from arterial baroreceptors, with the exception of neurons in the circumventricular organs surrounding the third ventricle that are activated by sustained hypotension. The latter group of neurons are known to project to vasopressin-secreting neurons in the supraoptic nucleus, and may therefore via this pathway trigger the hypotension-induced release of vasopressin that occurs in the absence of baroreceptor inputs.

Safety of Hymenoptera venom rush immunotherapy.

We studied 97 consecutive patients who had received Hymenoptera venom rush immunotherapy in our department. There were 53 males and 44 females, whose mean age was 46 years (8-74 years). Most study patients had experienced severe anaphylaxis induced by a Hymenoptera sting: the reaction was Müller stage IV in 48 patients. Skin tests were positive for Vespula venom in 85 cases, Polistes venom in 23, and bee venom in 23. Radioallergosorbent test values exceeded 0.70 kIU/l in 60 cases. Immunotherapy was performed with Vespula venom alone in 73 cases, bee venom alone in five cases, and both Vespula and bee venom in 19 cases. A cutaneous reaction was seen at the injection site in most patients. Four patients also had skin manifestations in areas remote from the injection site. Blood pressure elevation was seen in 11 patients, moderate hypotension in two, rhinitis in one, asthenia or headache in seven, visual disorders and vertigo in two, and transient dyspnea in two. Our protocol has proved very safe, epinephrine never being required in the 97 reported cases.

The influence of acute hypoxemia and hypovolemic hypotension of neuronal brain activity measured by the cerebral function monitor in newborn piglets.

Little is known about the cerebral electrical response to short periods of hypoxemia, hypotension and their combination. These conditions occur frequently in critically ill newborn infants; their cerebral electrical activity can be registrated easily with the Cerebral Function Monitor (CFM). Therefore we recorded on-line cortical electrical activity during hypoxemia and hypotension in 11 newborn piglets aged 13-18 days. Hypoxemia was induced by reducing inspired oxygen fraction. Hypotension was induced by withdrawal of blood. The experimental groups were: Group I: arterial oxygen saturation (SaO2) 45-85%, group II: SaO2 < 45%, group III: mean arterial pressure (MAP) 50-75 mmHg, group IV: MAP < 50 mmHG, group V: SAO2 < 85% and MAP 50-75 mmHg and group VI: SaO2 < 85% and MAP < 50 mmHg. CFM registrated normal cortical electrical activity during periods of moderate or severe hypoxemia (group I and II) and during isolated moderate hypotension (group III). The cortical activity decreased significantly due to severe hypotension alone (group IV) and combined hypotension and hypoxemia (group V and VI). Hypotension has a more potent effect on cortical electrical activity than hypoxemia in the newborn piglet. Cerebral electrical activity does not change during severe hypoxemia and moderate hypotension possibly due to cerebral flow regulation. CFM recorded decreased cerebral electrical activity during severe hypotension and hypotension with hypoxemia. CFM could provide invaluable data in severely ill newborns.

Stability of high-energy phosphates in right ventricle: myocardial energetics during right coronary hypotension.

This study was conducted to determine if mechanisms that reduce right coronary (RC) blood flow (RCBF) and right ventricular (RV) oxygen consumption (MVO2) during moderate RC hypotension preserve RV high-energy phosphates. RC arteries of anesthetized dogs were cannulated and perfused with arterial blood supplied by a pressurized extracorporeal circuit. RC perfusion pressure (RCPP) was either kept constant at 100 mmHg or reduced to 60 or 30 mmHg for 20 min followed by a freeze-clamp biopsy of RV. Left ventricular (LV) biopsy was also performed to compare energy metabolism between RV and LV.RCBF and MVO2 significantly decreased when RCPP was reduced to 60 mmHg, but RV segment shortening (%SS) was unchanged; ATP, creating phosphate (CrP) and phosphorylation state of CrP ([CrP]/[Cr][Pi]) did not differ from control values. RV %SS, CrP, and phosphorylation state fell markedly at 30 mmHg RCPP. At 100 mmHg RCPP, CrP phosphorylation state in RV was only 35% of that in LV. These results indicate that RV increases its energetic efficiency without significant changes in high-energy phosphates or CrP phosphorylation state during moderate RC hypotension. Furthermore, the RV myocardium maintains a much lower energy level than LV myocardium, commensurate with its lower energy requirements.

Autologous Platelet-Rich Plasmapheresis

Preoperative platelet-rich plasmapheresis has been suggested as a means of reducing homologous blood transfusions in cardiac surgical patients. The current study evaluated this technique in patients undergoing repeat cardiac operations. Fifty-two patients undergoing repeat myocardial revascularization and/or valve replacement were evaluated in a prospective randomized controlled study design. Autologous platelet-rich plasma (PRP) was harvested after the induction of anesthesia in the experimental group. After reversal of heparin, each patient received his or her autologous plasma. Patients in the control group did not have plasmapheresis and received standard transfusion therapy if coagulation variables were abnormal and a coagulopathy was clinically evident. Routine coagulation tests, thromboelastography (TEG), perioperative bleeding, and transfusion requirements were compared in the two groups. Forty-four patients completed the study. A significantly larger volume of packed red blood cells (PRBCs) was transfused in the PRP group than in the control group (P = 0.03). Platelet and fresh frozen plasma (FFP) transfusions did not differ between the two groups. Mediastinal tube drainage did not differ between the two groups. During PRP infusion, 60% of the patients required treatment for moderate hypotension (mean arterial pressure [MAP] < 60 mm Hg). Only 16% of control patients required treatment for hypotension during the comparable time period (P < 0.05). No patient who completed the study returned to the operating room for postoperative bleeding. These data suggest that PRP did not reduce postby-pass bleeding or transfusion requirements in repeat cardiac surgical patients. Moreover, the incidence of hypotension during PRP reinfusion introduces a potential risk to the procedure in the absence of any obvious benefit.

Differential microcirculation dynamics during deliberate hypotension induced by nicardipine, PGE1 and trimethaphan in rat mesentery

The purpose of this study was to determine the arteriolar changes that occur in the microcirculation during deliberate hypotension and general anaesthesia and whether the changes depended on the drugs used to induce vasodilatation or on the degree of systemic blood pressure decrease. Changes in the vessel diameter and the velocity of red blood cells in the mesenteric arterioles of pentobarbitone-anaesthetized rats were observed using continuous biomicroscopy. Observations were made during deliberate moderate (BP 70 mmHg) or deep (BP 50 mmHg) hypotension by titration with nicardipine, prostaglandin E1 (PGE1) or trimethaphan. Then, the responses of arterioles to locally applied noradrenaline (1 microgram) were assessed. During moderate hypotension PGE1 decreased the arteriole diameter slightly (16.7 +/- 1.6 to 14.7 +/- 1.3 microns, P < 0.05), reduced the velocity of red blood cells considerably (1.98 +/- 0.2 to 1.03 +/- 0.4 mm.sec-1, P < 0.05) and increased the contractile response of arterioles to locally-applied noradrenaline. Nicardipine and trimethaphan had no effect on the microcirculation. During deep hypotension, all drugs decreased the diameter of the arterioles slightly but reduced the velocity of red blood cells considerably (P < 0.05). We conclude that the major change in the mesenteric arterioles during deliberate hypotension during general anaesthesia is a decrease in red blood cell velocity that is dependent on the drug used and the degree of blood pressure decrease.

Autologous Platelet-Rich Plasmapheresis

Preoperative platelet-rich plasmapheresis has been suggested as a means of reducing homologous blood transfusions in cardiac surgical patients. The current study evaluated this technique in patients undergoing repeat cardiac operations. Fifty-two patients undergoing repeat myocardial revascularization and/or valve replacement were evaluated in a prospective randomized controlled study design. Autologous platelet-rich plasma (PRP) was harvested after the induction of anesthesia in the experimental group. After reversal of heparin, each patient received his or her autologous plasma. Patients in the control group did not have plasmapheresis and received standard transfusion therapy if coagulation variables were abnormal and a coagulopathy was clinically evident. Routine coagulation tests, thromboelastography (TEG), perioperative bleeding, and transfusion requirements were compared in the two groups. Forty-four patients completed the study. A significantly larger volume of packed red blood cells (PRBCs) was transfused in the PRP group than in the control group (P = 0.03). Platelet and fresh frozen plasma (FFP) transfusions did not differ between the two groups. Mediastinal tube drainage did not differ between the two groups. During PRP infusion, 60% of the patients required treatment for moderate hypotension (mean arterial pressure [MAP] < 60 mm Hg). Only 16% of control patients required treatment for hypotension during the comparable time period (P < 0.05). No patient who completed the study returned to the operating room for postoperative bleeding. These data suggest that PRP did not reduce postbypass bleeding or transfusion requirements in repeat cardiac surgical patients. Moreover, the incidence of hypotension during PRP reinfusion introduces a potential risk to the procedure in the absence of any obvious benefit. (Anesth Analg 1995;81:229-35)

Autologous Platelet-Rich Plasmapheresis

Preoperative platelet-rich plasmapheresis has been suggested as a means of reducing homologous blood transfusions in cardiac surgical patients. The current study evaluated this technique in patients undergoing repeat cardiac operations. Fifty-two patients undergoing repeat myocardial revascularization and/or valve replacement were evaluated in a prospective randomized controlled study design. Autologous platelet-rich plasma (PRP) was harvested after the induction of anesthesia in the experimental group. After reversal of heparin, each patient received his or her autologous plasma. Patients in the control group did not have plasmapheresis and received standard transfusion therapy if coagulation variables were abnormal and a coagulopathy was clinically evident. Routine coagulation tests, thromboelastography (TEG), perioperative bleeding, and transfusion requirements were compared in the two groups. Forty-four patients completed the study. A significantly larger volume of packed red blood cells (PRBCs) was transfused in the PRP group than in the control group (P = 0.03). Platelet and fresh frozen plasma (FFP) transfusions did not differ between the two groups. Mediastinal tube drainage did not differ between the two groups. During PRP infusion, 60% of the patients required treatment for moderate hypotension (mean arterial pressure [MAP] < 60 mm Hg). Only 16% of control patients required treatment for hypotension during the comparable time period (P < 0.05). No patient who completed the study returned to the operating room for postoperative bleeding. These data suggest that PRP did not reduce postbypass bleeding or transfusion requirements in repeat cardiac surgical patients. Moreover, the incidence of hypotension during PRP reinfusion introduces a potential risk to the procedure in the absence of any obvious benefit.

Ropivacaine: An experimental and clinical study with special reference to analgesic, circulatory and antiinflammatory effects

Aims of the study: 1. to compare ropivacaine, a new long-acting amino-amide local anaesthetic drug, and bupivacaine (with/without adrenaline) concerning dermal analgesia and local vascular effects, 2. to design a suitable test procedure to evaluate changes in skin blood flow after intradermal injection of local anaesthetics, 3. to evaluate changes in skin blood flow of various concentrations of ropivacaine with/without adrenaline, 4. to investigate the influence of ropivacaine, bupivacaine, lidocaine, mepivacaine and prilocaine on the production of oxygen metabolites in human polymorphonuclear leukocytes (PMNL) (intra- and extracellular reactions), and 5. to examine the neural blocking characteristics on sensory, motor and sympathetic pathways using ropivacaine for epidural analgesia.72 male patients scheduled for transurethral surgery and 50 male volunteers participated in this work. Heparinized blood was obtained from a total of 29 healthy adult blood donors.Dermal analgesia was evaluated by pin-prick, skin colour changes by visual inspection, skin blood flow by laser Doppler flowmetry, sensory blockade by pin-prick, motor blockade by a modified Bromage scale, sympathetic blockade by assessments of skin resistance level (SRL) and response (SRR), skin temperature and skin blood flow (laser Doppler flowmetry). Production of oxygen metabolites by PMNLs was measured by luminal-enhanced chemiluminescence (intra- and extracellular reactions).Ropivacaine produced significantly longer duration of dermal analgesia, following intradermal injection (0.1 ml, 30-G needle), compared with bupivacaine, in comparable concentrations. Addition of adrenaline increased the duration of both local anaesthetics. Local blanching was more frequent for plain solutions of ropivacaine.The effect of drugs on local circulation may well be studied by intradennal injection (0.1 ml, 30-G needle, volar surface, forearms) and recording of changes in skin blood flow (laser Doppler flowmetry). The intradennal injection of a local anaesthetic drug may produce not only a further increase but also a decrease in skin blood flow, if the effect of an intradermal saline injection, causing a very reproducible flow increase, is considered in the evaluation of the net circulatory effect of the tested drug.Intradermal injection of lidocaine 1% and bupivacaine 0.75% produced an increase in skin blood flow. Ropivacaine 1% produced a flow similar to saline, while a decrease was seen for ropivacaine 0.75%. Ropivacaine0.5%, 0.375%, 0.25%, 0.125% and 0.063% showed a gradual further reduction in flow, where 0.063% produced a flow similar to adrenaline-injection (5 Jlg/ml) and almost as low as at the untreated control sites. The combination of ropivacaine 1%, 0.5% , 0.25% and adrenaline did not accentuate but instead decreased the vasoconstrictive effect of adrenaline.By and large a decrease in response of chemiluminescence for PMNLs was seen with the higher concentrations of the various local anaesthetics. Lidocaine showed a minor decrease even at lower concentrations. Ropivacaine 1000 J.Lg/ml showed a depression of both intra- and extracellular responses that was similar to, and even somewhat more pronounced than lidocaine 1000 J.Lg/ml. This effect could be of great interest e.g. for local antiinflammatory effects by topical administration, but it has to be further investigated. A marked increase for prilocaine (1000 Jlg/ml) in intracellular response accompanied with a reduction in extracellular response was noted.Ropivacaine (0.5%, 0.75% with/without adrenaline) 20 ml administered epidurally provided a good sensory blockade and a motor blockade satisfactory for transurethral surgery. The maximum sensory level of analgesia was high, median Th 2-3. The majority of patients had a marked or complete sympathetic blockade in the lower limbs. Besides mild or moderate hypotension, which responded well to treatment with ephedrine, no other serious adverse reactions were seen, Addition of adrenaline did not provide any significant prolongation of the epidural blockade, and did not alter the influence upon the sympathetic blockade nor the hemodynamic changes during onset.

Sympatholytic effect of clonidine depends on the respiratory phase in rat splanchnic nerve

Peri-event averaging of the sympathetic nerve discharge was done to measure the magnitude of the sympatholytic effect of the anti-hypertensive drug clonidine during three different phases of the respiratory cycle (inspiration, I; postinspiration, post-I; late expiration, pre-I). Arterial pressure (AP) and discharges of splanchnic sympathetic (SND) and phrenic nerves (PND, onset used for peri-event averaging) were recorded in urethane-anesthetized, vagotomized, aortic deafferentated, paralyzed and artificially ventilated Sprague-Dawley rats ( n = 7). During control periods (mean AP 106 ± 10 mmHg) SND was distributed equally throughout the three selected respiratory periods, though two brief peaks were noted during the I and post-I periods. Low doses of clonidine (15–30 μg/kg i.v.) produced brief hypertension (< 30 s, 150 ± 9 mmHg at peak) followed by moderate hypotension (89 ± 3 mmHg) and a reduction in mean SND (−63 ± 11% from control value). High doses of clonidine (200–250 μg/kg i.v.) produced sustained hypertension (> 10 min, 173 ± 3 mmHg) and silence of SND. During this sustained hypertension, lowering AP by i.v. nitroprusside retrieved a component of SND that was barosensitive but insensitive to clonidine. During those hypotensive periods (spontaneous after a low dose of clonidine, and induced by nitroprusside after a high dose of clonidine), SND was most attenuated during the pre-I period and least during the I period. The I component of SND was significantly less attenuated than the post-I component by clonidine and, in most cases (6 out of 7), SND showed a single inspiratory peak following clonidine administration. It is concluded that ( i) the pre-I component of SND is the most sensitive to clonidine and ( ii) the I component of SND is the most resistant to the drug.

Differential patterns of local cerebral glucose utilisation associated with rilmenidine- or B-HT 933-induced hypotension

The anti-hypertensive drug, rilmenidine, has activity at both imidazoline-preferring receptors (IPRs) and α 2-adrenoceptors . However, available evidence suggests that its hypotensive effect is mediated via central IPRs. In the present study, the neuroanatomical regions involved in mediating the hypotensive response to rilmenidine were investigated using the [ 14C]2-deoxyglucose in vivo autoradiographic technique to map drug-induced changes in glucose utilisation within the CNS of conscious, spontaneously hypertensive rats (SHR). The cerebral metabolic effects of rilmenidine were compared with those of B-HT 933, a selective, α 2-adrenoceptor agonist with no selectivity for the IPR. Rilmenidine (1 mg/kg, s.c.) and B-HT 933 (2 mg/kg, s.c.) both elicited a moderate but significant hypotension ( −24±2 and −18±5mmHg, resp.) and bradycardia ( −62±19.5 and −69±14 beats/min, resp.). [ 14C]2-deoxyglucose autoradiography, initiated after stabilisation of the drug-induced reduction in blood pressure, revealed significant reductions ( P < 0.05) in local cerebral glucose utilisation (LCGU) in the intermediolateral cell column of the spinal cord, area postrema, ventrolateral medulla, nucleus tractus solitarius and cuneate nucleus of rilmenidine-treated rats. Rilmenidine did not significantly alter LCGU in a number of structures containing high densities of α 2-adrenoceptors such as nucleus accumbens, locus coeruleus, frontal cortex. No significant changes in glucose use were evident in any of the 26 CNS regions examined following B-HT 933 administration. These results provide evidence for the functional involvement of brainstem cardiovascular control centres in the central hypotensive effects of rilmenidine. In addition, the neuroanatomical localisation of rilmenidine-induced glucose use changes in relation to the distributions of IPR and α 2-adrenoceptor binding sites, further supports the involvement of IPRs in the hypotensive response to rilmenidine.

Spinal anesthesia with meperidine as the sole agent for cesarean delivery.

Meperidine is an opioid with local anesthetic properties that produces spinal anesthesia after subarachnoid injection for surgical procedures. The aim of this study was to evaluate the clinical relevance of spinal meperidine for cesarean delivery. Twenty-eight ASA I-III parturients scheduled for cesarean delivery were included in the study. Meperidine 1 mg/kg was administered subarachnoid. Patients were monitored for appropriate anesthesia and side effects. Cesarean delivery was successfully performed under spinal meperidine in 22 cases: two cases required general anesthesia before incision and the duration of sensory anesthesia was too short in four cases. Side effects included moderate hypotension (decrease in arterial blood pressure > 30 mm Hg in 36% of the cases), nausea (32%), and pruritus (10.7%). No respiratory depression was documented in mothers and newborns. Although short-acting, meperidine can be used as a substitute for local anesthetics for cesarean delivery, especially when local anesthetics are not available.

Changes in the neural drive to abdominal expiratory muscles in hemorrhagic hypotension.

The purpose of this study was to test the hypothesis that hemorrhage-induced hypotension increases the neural drive to the abdominal expiratory muscles in chloralose-urethan-anesthetized cats that are studied under conditions of constant arterial PCO2 (PaCO2) and hyperoxia. A secondary aim was to describe in detail the concomitant changes in inspired pulmonary ventilation (VI) and the pattern of breathing under these conditions. The rectified and integrated electromyogram (EMG) of the external oblique and rectus abdominis muscles and VI were recorded in moderate and severe hemorrhagic hypotension, leading to reductions in mean blood pressure of approximately 30 and 60%, respectively. The PaCO2 was prevented from falling, and the arterial PO2 was maintained at a hyperoxic level (> 200 mmHg) by adding CO2 and O2 to the inspired gas mixture. VI increased by 2.5- and 5-fold in moderate and severe hypotension (P < 0.05). The changes in VI were mediated exclusively by changes in tidal volume, indicating that the reflex did not alter the activity of respiratory rhythm-generating structures. The EMG of external oblique muscles averaged 2, 44, and 100% in control conditions and in moderate and severe hypotension, respectively; corresponding values in rectus abdominis muscles were 10, 28, and 100% (P < 0.05 for both muscles). Bilateral cervical vagotomy caused a one- to three-fold decrease in the ventilatory response to hemorrhage and abolished the increase in abdominal muscle EMG activities. In conclusion, hemorrhagic hypotension reflexly increases pulmonary ventilation and the neural drive to the abdominal muscles. The reflex is vagally mediated, but the location of the receptors was not identified.

Pretreatment of transient focal cerebral ischemia in rats with the calcium antagonist AT877.

The efficacy of pretreatment with the recently developed intracellular calcium antagonist AT877 against transient focal cerebral ischemia was investigated in rats subjected to middle cerebral artery occlusion and reperfusion using the endovascular suture method. Halothane-induced moderate hypotension (60 mm Hg) was used during 100 minutes of temporary middle cerebral artery occlusion. In the treated animals (n = 10), an intravenous infusion of AT877 (0.03 mg/kg per minute) was initiated 30 minutes before the ischemic event and continued during the ischemic period. The control rats (n = 10) received physiological saline in a similar fashion. Local cerebral blood flow was measured by the hydrogen clearance technique. Neurological examinations were performed daily during the 48-hour observation period, and infarct size was assessed by triphenyltetrazolium chloride staining. A continuous infusion of AT877 significantly improved local cerebral blood flow during ischemia. The treated animals showed a better neurological outcome after a 24-hour observation period, and a significant reduction in ischemic brain injury resulted in both the neocortex (149 +/- 20 versus 41 +/- 14 mm3, P < .01) and the striatum (80 +/- 5 versus 46 +/- 8 mm3, P < .05). The size of the neocortical infarct was reduced, with increasing mean ischemic cerebral blood flow in the control and treated animals (r = .923, P = .0001). AT877 pretreatment was effective in preventing brain injury during transient focal cerebral ischemia and improving neurological status. This beneficial effect seems to be mediated, in part, by its primary action of increasing cerebral blood flow.