Neurogenic pathways in remote ischemic preconditioning induced cardioprotection: Evidences and possible mechanisms

Remote ischemic preconditioning (RIPC) is an intrinsic phenomenon whereby 3~4 consecutive ischemia-reperfusion cycles to a remote tissue (noncardiac) increases the tolerance of the myocardium to sustained ischemiareperfusion induced injury. Remote ischemic preconditioning induces the local release of chemical mediators which activate the sensory nerve endings to convey signals to the brain. The latter consequently stimulates the efferent nerve endings innervating the myocardium to induce cardioprotection. Indeed, RIPC-induced cardioprotective effects are reliant on the presence of intact neuronal pathways, which has been confirmed using nerve resection of nerves including femoral nerve, vagus nerve, and sciatic nerve. The involvement of neurogenic signaling has been further substantiated using various pharmacological modulators including hexamethonium and trimetaphan. The present review focuses on the potential involvement of neurogenic pathways in mediating remote ischemic preconditioning-induced cardioprotection.

An experimental study of artificial murine bladder reflex arc established by abdominal reflex / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The neurogenic bladder dysfunction caused by spinal cord injury is difficult to treat clinically. The aim of this research was to establish an artificial bladder reflex arc in rats through abdominal reflex pathway above the level of spinal cord injury, reinnervate the neurogenic bladder and restore bladder micturition.</p><p><b>METHODS</b>The outcome was achieved by intradural microanastomosis of the right T13 ventral root to S2 ventral root with autogenous nerve grafting, leaving the right T13 dorsal root intact. Long-term function of the reflex arc was assessed from nerve electrophysiological data and intravesical pressure tests during 8 months postoperation. Horseradish peroxidase (HRP) tracing was performed to observe the effectiveness of the artificial reflex.</p><p><b>RESULTS</b>Single stimulus (3 mA, 0.3 ms pulses, 20 Hz, 5-second duration) on the right T13 dorsal root resulted in evoked action potentials, raised intravesical pressures and bladder smooth muscle, compound action potential recorded from the right vesical plexus before and after the spinal cord transaction injury between L5 and S4 segmental in 12 Sprague-Dawley rats. There were HRP labelled cells in T13 ventral horn on the experimental side and in the intermediolateral nucleus on both sides of the L6-S4 segments after HRP injection. There was no HRP labelled cell in T13 ventral horn on the control side.</p><p><b>CONCLUSION</b>Using the surviving somatic reflex above the level of spinal cord injury to reconstruct the bladder autonomous reflex arc by intradural microanastomosis of ventral root with a segment of autologous nerve grafting is practical in rats and may have clinical applications for humans.</p>

Emergência hipertensiva / Hypertensive emergencies

A emergência hipertensiva é uma condiçäo de risco iminente de vida caracterizada por elevaçäo súbita da pressäo arterial e comprometimento de órgäo-alvo. O cérebro, coraçäo, rins, retina e aorta säo alvos frequentes. Säo importantes a presteza diagnóstica e o tratamento precoce. Dá-se escolha aos anti-hipertensivos parenterais de açäo rápida e de curta duraçäo, evitando-se, porém, quedas pressóricas que comprometam a perfusäo de órgäos ou sistemas. O objetivo desta revisäo é mostrar como se diagnostica e se trata precocemente a emergência hipertensiva.

Plasma renin-angiotensin activity [PRA] and cardiovascular responses during deliberate hypotention

A safe hypotensive technique should be easy to control, doesn't alter vital organ blood flow and can suppress or prevent increase in plasma renin angiotensin [PRA] and its untowards effects, The aim of this work is to demonstrate if PRA level differ according to the hypotensive agent used in two comparable groups using either sodium nitroprusside-trimetaphan mixture 1:10 [TNP] G I or isoflurane 0.75-4% G II as a method for deliberate hypotension and to demonstrate which of them is the more acceptable technique. 60 adult patients ASA class I or II were included in the study. The study showed that TNP mixture was effective as isoflurane in inducing rapid and smooth hypotension it was more rapid same for the recovery time. The mean arterial blood pressure were maintained with insignificant increase in heart rate for both groups all over the hypotensive period. No significant changes observed in ECG, blood gases [PaO2, PaCO2, SaO2], acid base [pH, BE, HCO3], or heamatological parameters [HB%, bleeding time, platelet count, clot retraction, prothrombin concentration]. Plasma renin activity [PRA] showing a significant rise in both groups [group I] 77.6%, [group II] 88% rising more for the isoflurane group denoting less control. So PRA level can be used as a reflection of resistance mechanism for induced hypotension and may aid a bit how to manipulate the used dose of the hypotensive agent. TNP mixture have been shown to produce lower levels of PRA increase, with no signs of resistance, or tachyphelaxis seen with isoflurane [two cases], with a cheaper price

Crisis hipertensivas / Hypertensive crisis

La cisis hipertensiva, afortunadamente es una complicacion relativamente rara de la hipertension arterial. El cuadro clinico es reconocido por valores de presion arterial elevados y sintomas cardiovasculares, neurologicos y visuales progresivos, y en algunos casos con falla renal y trastornos hematologicos concomitantes. Una vez diagnosticado, el paciente es hospitalizado en una unidad de cuidados intensivos, para el inicio rapido de la terapia hipotensora y las medidas terapeuticas alternas. Una vez controlada la presion arterial y si las condiciones clinicas del paciente lo permiten, se iniciara la medicacion oral. Los resultados obtenidos con las anteriores medidas terapeuticas han sido satisfactorios a medida que se adquiere mas experiencia con el uso de nuevos farmacos y se obtiene un mejor pronostico para estos pacientes. Se quiere resaltar que una vez diagnosticada la crisis hipertensiva se necesita de una atencion rapida y adecuada para un mejor control de la presion arterial

Control of Intraoeular Pressure by Intravenous Lidocaine Pretreatment / 대한마취과학회지

It is a known fact that the increase of intraocular pressure results from the action of succinylcholine, endotracheal stimulation to carina, bucking and coughing etc during the induction arid recovery periods. Efforts have been made by several inveatigators to prevent intraocular hypertension by giving trimetaphan, inderal or curare. However, their effects were not remarkable. In this study, lidocaine Img/tg was administered intravenously to selectee patients 2-3 minutes hefore induction ; followed by regular induction with pentothal, succinylcholine and incubation. Intraocular pressures were measured at the pre-induction and post-intutation time, and every 30 minutes until the early recovery period, thereafter. The result of this study showed that the post-intubational increase of intraocular pressure was prevented in 86.7% of the lidocaine pretreated cases. The increase of post-extuba-tional intraocular pressure was also reduced significantly in the lidocaine pretreated group-as well. We came to the conclusion that lidocaine pretreatment technic can be used effectively to prevent intraocular hyperteilsion caused by induction and extubation in clinical practice.

A Clinical Evaluation of Hypotensive Anesthesia for Intracranial Aneurysm Surgery / 대한마취과학회지

Deliberately induced hypotension reduces bleeding in operative fields, therby facilitating the surgical manipulation of a highly vascularized lesion and enabling a better dissection to be made. Hypocapnia is a technique by which the regional cerebral blood flow is reduced, effecting a decrease in the intracranial volume. The monitoring of end-tidal CO2 tension(PECO2) is widely done since the amount of end-tidal CO2 tension reflects indirectly the value of the degree of arterial CO2 tension(PaCO2). During hypotension, increased physiologic dead space my produce the widened PaCO2-PECO2 gradient and this large gradient makes PECO2 an unreliable indication of PaCO2. There are many reports on hypotensive agents and techniques. Induced hypotension with halothane has been reported to be a relatively safe and useful method by Murtagh(1960) and Schettini, et al (1967). We reported 100 cases of halothane induce hypotensive anesthesia for intracranial aneurysm surgery in 1979. The present study reports concerning the hypotensive anesthesia for 259 cases of intracranial aneurysm surgery, which were performed at Severance Hospital of the Yonsei University College of Medicine from 1972 to 1985. We evaluated prospectively the PaCO2-PECO2 gradient with modern infrared capnographs during the induced hypotension of 25 cases, which was performed for intracranial aneurysm surgery at this hospital. The result of the retrospective and prostpective studies were as follows. A. Retrospective study 1) Halothane and enflurane were used as the primary anesthetics in 246 and 13 cases, respectively. Hydralasine, nitroprusside, and trimetaphan were supplementarily used for inducing hypotension in 29, 19 and 15 cases, respectively. 2) The mean arterial blood pressure of the lowest blood pressure in the induced hypotension group was 57.2+/-9.3 mmHg, and the mean arterial blood pressure of the highest blood pressures during the induction fo anesthesia was 111.3+/-20.8mmHg. 3) There was no significant difference in the perioperative hemoglobins, hematocrits, and serum electrolytes. 4) In the introperative period gas analysis revealed respiratory alkalosis(arterial CO2 tension and pH were 29.7+/-6.7mmHg and 7.485+/-0.078, respectively). In other values there was no significant change. 5) The mortality rate in 259 cases of intracranial aneurysm surgery was 6.2%. B. Prospective study There was no significant difference in the PaCO2-PECO2 gradients between in the hypotensive period (5.5+/-3.8 mmHg) and in the normotensiveperiod(4.3+/-3.4mmHg). In conclusion, the technique of using induced hypotension with the inhalation anesthetics, halothane or enflurane, is a safe and useful one to use in performing surgery for intracranial aneurysm, and end-tidal carbon dioxide tension can be used as an indirect measure of arterial carbon dioxide during the induced hypotension.

The Effects of Trimethaphan on Responses of the Cardiovascular System During Endotracheal Intubation / 대한마취과학회지

Tachycardia and hypertension are well documented complications of laryngoscopy and tracheal intubation in normal patients(Reid and Brace, 1940; Burstein et al, 1950; King et al 1951; Takeshima et al, 1964; Forbes and Dally, 1970). This phenomenon has been studied in detail in cats by Tomori and Widdicombe(1969), who found it to be associated with an increased impulse traffic in the cervical sympathetic efferent fibers. This nervous activity was especially increased by stimulation of the epipharyngeal and laryngopharyngeal regions, and was accompanied by the largest hypertensive response(Takki et al, 1972). Also various arrhythmias were elicited by vagal stimulation during endotracheal intubation(Burstein et al, 1950: King et al, 1951; Forbes et al, 1970), and it has been known that cardiac arrest could be observed in severe cases(Burstein et al, 1950; Dwyer, 1953; Raffan, 1954; Lander and Mayer, 1965). That hypertension during induction of anesthesia in critically ill patients may be harmful is substantiated by reports of cerebral hemorrhage, left ventricular failure and life threatening cardiac arrhythmia(Forbes and Dally, 1970; Dingle, 1966; Masson, 1964; Katz and Bigger, 1970). Pharmacologic attempts to attenuate these blood pressure and heart rate elevations and appearances of arrhythmia have been tried but theese approaches have been only partially successful. We selected at random 60 adult patients who had received operation under the general anesthesia with intubation at Severance Hospital from August to September, 1979. They were divided into 4 groups. Group l was normotensive without trimethaphan(n=20), Group ll was normotensive with trimethaphan(n=20), Group ll was hypertensive without trimethaphsn(n=10) and Group lV was hypertensive with trimethaphan(n=10). The changes of arterial blood pressure and pulse rate, and appearance of arrnythmia were analyzed and data were compared between groups. The results were as follows; 1. In the trimethaphan injected group, during induction attenuation of increase in blood pressure was not significant in the normotensive group but was statistically significant in the hypertensive group. 2, The effects of trimethaphan on changes of pulse rate were not significant during laryngoscopic insertion under general anesthesia. 3, On EKG of hypertensive patients the trimethaphan injected group revealed fewer abnormal EKG findings than the control group. It is suggested from the above results that intravenous injection of a small amount(0.1 mg/kg) of trimethaphan in a hypertensive patient just before endotracheal intubation can be used as one method to prevent a dangerous hypertensive crisis.

The Clinical Experiences of Induced Hypotension with Halothane and Trimetaphan combined with Halothane for Cerebral Aneurysm Surgery / 대한마취과학회지

Induced hypotensive anesthesia is well known anesthetic method. It reduces bleeding into surgical field and provides better visibility for the surgery of cerebral aneurysm. The most current method for induced hypotensive anesthesia is composed of general anesthesia and ganglionic blockade. This study was performed to compare the clinical experience from hypotensive anesthesia with halothane only to hypotensive anesthesia with trimetaphan and halothane. The results of our study were as follows; 1) There are no different technical difficulties during hypotensive anesthesia between halothane induced cases and trimetaphan used cases. 2) No clinical evidence of direct organic damage because of hypotensive anesthesia was found. 3) The prognosis of postoperative recovery may deeply related to preoperative physical state than anesthesia. To conclude through this experience, induced hypotensive anesthesia is a useful method for the cerebral aneurysmal surgery. The technique of deliberate hypotension is not too difficult to use in ordinary equiped hospital.

The Effect on Inhibition of Raising Intraocular Pressure during Endotracheal Intubation in Man / 대한마취과학회지

After various anesthetic inductions, the effects of tracheal intubation on mean arterial preasure(MAP) and intraocular pressure(IOP) were studied in 88 random patients who did not have any cardiovascular and ocular diseases properatively. IOP and MAP were measured with a Perkins hand held applanation-tonometer and a Cardi- 8- mini syhygmomanometer respectively. The results were as follows: 1) Both the MAP and IOP were increased in succinylcholine and pancuronium anesthetic induction groups after endotracheal intubation. 2) Rises in,both the MAP and IOP were inhibited in induced hypotensive anesthetic induction with halothane and trimethaphan. 3) The IOP was inhibited in the propranolol group. These results show the superiority of induced hypotensive anesthetic induction with halothane, trimethaphan and propranolol prior to administration for inhibition of raising intraocular pressure.

A Clinical Study of Halothane Induced Hypotension for Intracranial Aneurysm Surgery / 대한마취과학회지

For lesions like intracranial aneurysms which are located near highly vascularized regions, adequate dissection becomes almost impossible unless local blood flow can be reduced. Deliberate hypotension, purposefully lowering the arterial pressure to a level at which bleeding is no longer a problem, facilitates surgery, allows performance of a better dissection, and shortens the length of the procedure. Currently, the most useful method for induced hypotensive anesthesia is the use of chemical drugs, such as trimethaphan, nitroprusside and halothane. Induced hypotension with halothane has been reported to be a relatively safe and useful method by Murtagh (1960) and Schettini, et al (1967). Halothane has the effect of depression of myocardial contractility, central autonomic inhibition, ganglionic blocking action and suppression of the peripheral actions of norepinephrine and direct vasodilation on the vessel wall. The advantage of halothane is the reduction of mean arterial pressure slowly (1-3 mm Hg/min) and it has a transient effect on EKG, little effect on brain cortical function and appropriate oxygen supply to brain tissue. The halothane induced hypotension in 100 cases of intracranial aneurysm surgery, which were performed at Severance Hospital of the Yonsei University College of Medicine from .1972 to 1977, was investigated clinically. The results of our study were as follows: 1) The locations of intracranial aneurysm in order were the anterior cerebral artery (37 cases), internal carotid artery (35 cases), middle cerebral artery (23 cases) and posterior cerebral artey (2 cases). Three cases of multiple cerebral aneurysm were found in our study. 2) In the hypotensive phase, the mean systolic and diastolic pressures were 73. 45 mmHg+/- 0. 86, 54. 95 mmHg+/- 0. 86 and the mean duration was 34. 74 min+/- l. 60. 3) The blood pressure control by halothane was comparatively easy and there was no cliaical evidence of direct injury to the brain, heart, kidney and liver due to halothane induced hypotension. 4) The mortality rate in the 100 cases of the intracranial aneurysm was 16 percent. From the above observation it may be concluded that the technique of deliberate hypotension induced by halothane anesthesia is a useful method in the surgery of intracranial aneurysm.

The Changes of Cerebral Hymodynamics During Induced Hypotensive Anesthesia

An induced hypotension is employed as a useful technique for operations on intracranial aneurysms, brain tumors and other intracranial lesions to diminish operative bleeding and to decrease brain tension. In aneurysm surgery under induced hypotension, the sac becomes softer and thus diminishes the risk of rupture when clips are applid. In 1946 Gardner used arteriotomy to lower blood pressure by decreasing the blood volume during brain tumor surgery, then gradually improved. Pharmacologically-induced hypotension soon became the cominant method of producing hypotension. Halothane and trimethaphan are the most popular drugs for this purpose. On the other hand, the risks of hypotension are obvious. These include decreased cardiac output, decreased cerebral blood flow, and low perfusion pressure exposing brain tissue to the risk of hypoxia thereby aggravating the effects of the circulatory disturbance present in the brain lesion. In this situation the blood oxygen tension in jugular-bulb and lactate content in brain tissue have been found to be reliable indices of degrees of cerebral oxygenation. Consequently, several investigators have studied the critical level of arterial blood pressure during hypotensive anesthesia and have accepted 60 mmHg of systolic pressure(40~50 mmHg of mean arterial pressure) as a clinically applicable level free from the danger of cerebral hypoxia. Furthermore, Griffiths and Gillies(1948) postulated that systolic pressure over 30 mmHg would provide adequate tissue oxygenation. However, there are only a few reports concerning the adequacy of cerebral oxygenation under such low levels of arterial blood pressure. The purpose of this study is to investigate cereral hemodynamics and metabolism during halothane-induced hypotensive anesthesia and to find any evidence of cerebral hypoxia at the levels of 60 mmHg and 30 mmHg, of systolic blood pressure. 15 adult mongrel dogs, weighing 10~13kg, were anesthetized with intravenous pentobarbital sodium. Endotracheal intubation was performed. One femoral artery was cannulated with a polyethylene tube for arterial blood sampling. The tube was connected to a Statham pressure transducer for continuous arterial blood pressure recording. The common carotid artery was exposed and a probe of square-wave electromagnetic flowmeter was placed on the vessel to record the carotid blood flow. An electrocardiogram and above two parameters were recorded simultaneously on a 4-channel polygraph. The internal jugular vein was cannulated and a catheter threaded up to the jugular-bulb for sampling of venous blood draining from the brain. The cisterna magna was punctured with an 18 gauge spinal needle to sample the cerebrospinal fluid. The experiments were divided into control phase, induction phase, hypotensive phase I, hypotensive phase II, and recovery phase. Each phase was maintained for 30 minutes. Cerebrospinal fluid, arterial venous blood were sampled at the end of each phase for analysis of gas tension and lactate content. 100% oxygen was inhaled during the induction phase. During the hypotensive phases, halothane/O2 was administered to lower the arterial blood pressure. In the hypotensive phase I and hypotensive phase II systolic pressure was maintained at 60 mmHg and 30 mmHg, respectively. In the recovery phase, halothane was discontinued and 100% oxygen only was inhaled. The results obtained are summarized as follows; 1. The carotid artery blood flow, which represents the cerebral blood flow, decreased linearly during the decline of the arterial blood pressure. At the end of each phase there was no difference in the carotid blood flow between hypotensive phase I and phase II. Cerebral vascular resistance was markedly reduced in the hypotensive phase II, which suggests cereral vasodilation. 2. Cerebral venous pO2 decreased significantly in the hypotensive phases, but the values till remained within normal limits. A marked reduction of arterial pCO2 was noted in the hypotensive phases. The values approach the lower limits of safety. 3. The most outstanding difference between hypotensive phase I and II is in the lactate content of cerebral venous blood and cerebrospinal fluid. There was a moderate increase of lactate content, and a slight reduction of cereral venous pH in hypotensive phase II, however, a significant degree of cerebral hypoxia and metabolic acidosis could be excluded. 4. Most of the changes in the cerebral metabolism and hemodynamics including arterial blood pressure, tent to return to return to normal at the end of the recovery phase. From the result of this study, it is concluded; Halothane-induced hypotensive anesthesia at 60 mmHg of systolic blood pressure(45 mmHg of possibility of mild metabolic acidosis 30 mmHg of systolic blood pressure(23 mmHg of mean arterial pressure), adequate cerebral oxygenation is maintained without difficulty.

A Report of Unusual Anesthetic Managements of Pheochromocytoma / 대한마취과학회지

It has been emphasized that continuous monitorings of arterial pressure, central venous pressure, electrocardiogram, blood gas analysis, serum electrolytes, body temperature, hematacrit and urinary output are mandatory for the anesthetic management of pheochromocytoma. In addition, it is necessary for the anesthetists to understand pharmacologic effects of drugs which influence the peripheral vascular tone and cardiac excitability. We experienced recently anesthetic management of two cases of pheochromocytoma; one raised problems of ventricular arrhythmias and hypertension that aggravated nature of arrhythrmias by increasing blood pressure and responded favorably to treatment with propranolol and trimetaphan. Tumor of this case originated from abdominal aortic wall. The other was managed by injection of d-tubocurarine which induced narrowing of pulse pressure by depletion of increasing systolic pressure and accompanied tachycardia without cardiac decompensation. We have reported proper anesthetic managements of two cases of pheochromocytoma with N2O O2-halothane anesthesia and reviewed literatures in discussion.

Analysis of Laboratory Data on Induced Hypotension with Trimetaphan for Cerebral Aneurysm Surgery / 대한마취과학회지

Hypothermia and/or hypotensive anesthesia are well known technics for surgery of cerebral aneurysm. This study was performed to compare the Iaboratory data from hypotensive anesthesia with trimetaphan (Arfonad) to hypothermic anesthesia without trimetaphan for surgery of cerebral aneurysm For this purpose, the author performed hypotensive anesthesia with trimetaphan. Laboratory data studied were blood gases, hemoglobin, hematocrit, blood chemistry, urine output, specific gravity of urine, dose of trimetaphan, period of hypotensive state and dose of mannitol, etc. Laboratory data were obtained before surgery (Group A), hypotensive period (systolic blood pressure; 50~60 mmHg) (Group B) and immediately after the surgery (Group C) and were analysed. The results of analysis were as follows; 1. In gas studies, metabolic alkalosis and respiratory alkalosis were shown before surgery and the hypotensive period. Metabolic alkalosis and respiratory acidosis were shown after surgery. It is hard to imagine an explanation for the data. Metabolic acidosis and compensatory respiratory alkalosis should be expected due to decreased tissue perfusion by hypotension, presumably. 2. In Hb. and Hct. studies, among the 3 groups shown there was statistical significance (p( 0.001), but no clinical significance was noticed. 3. In blood chemistry; Serum K showed significant decrease (p<0.001) in the hypotensive period and immediate postoperative period compared with before surgery. Serum Na showed significant decrease (p<0.05) in the hypotensive period and significant increase (p<0.001) in the immediate postoperative period. Serum creatinine showed significant increase (p< 0.001) in the hypotensive and immediate postoperative period. Serum NPN showed significant decrease (p<0.001) in the hypotensive period compared with before surgery and the immediate postoperative period, but statistical significance was noticed in the hypotensive period only. There was no clinical significance among the 3 groups. 4. In urine output, significant decrease was noticed in the hypotensive and postoperative periods: but no statistical significance was found. 5. In specific gravity of urine, progressiv increase was found in the hypotensive and postoperative period than before surgery. 6. In ECG study, no significance change was noticed except one atrial premature contraction during hypotensive period. 7. All the above data were suggested no cerebral hypoxia and/or renal failure were encountered. 8. The mean trimetaphan dose was 189.50+/-172.73 mg, the mean mannitol dose was 53.75+/-13.75 g and the mean hypotensive period was 40.50+/-20.91 minutes respectively. In the statistical significance, unreasonable explanations were encountered. And also, clinically significant results were encountered among the non-statistical significance. To conclude through this study, when we present to give a results of statistical significance, there must be needed more careful analysis not only of obtained data but also analysis with more variable aspects, so further study is indicated.

Trimethaphan Camphorsulfonate in the Treatment of Shock / 대한마취과학회지

Trimethaphan camphorsulfonate (Arfonad), in 0.1 per cent concentration, has been administered slowly by intravenous drip to 6 patients in shock and protracted vasoconstrictive states. Administration of Arfonad results in vasodilation and relative hypovolemia. Blood or plasma expander was required to avoid an unacceptable hypotension. All patients survived except one, in whom the cause of death was not related .in any way to the use of Arfonad. Importance of supplementing respiration with oxygen and monitoring central venous pressure has been stressed and the rational use of both vasoconstrictor and vasiodiator discussed. At times, vasodilation is desirable, at other times, it may best be avoided. It is suggested that Arfonad may have a place in the treatment of shock but if so, it should be used only when protracted vasoconstriction exists.