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Objectives Spinal cord ischemia secondary to trauma or a vascular occlusive event is a threatening phenomenon. The neuroprotective properties of minocycline have been shown in several models of central nervous system diseases and after spinal cord ischemia; however, the benefit of using the drug requires additional confirmation in different animal models. Astrocytes are essential as regulators of neuronal functions and for providing nutrients. The authors hypothesized that astrocytes in the spinal cord may be an important target for minocycline action after ischemia and thus in the prevention of secondary spreading damage. Design A prospective, randomized animal study. Setting University research laboratory, single institution. Participants Adult male Sprague Dawley rats, weighing between 400 and 450 g. Interventions A model of spinal cord ischemia in the rat was used for this study to determine whether a single, high-dose (10 mg/kg) of minocycline protects against damage to the neuronal cytoskeleton, both in the white and gray matter, and whether it reduces glial fibrillary acidic protein levels, which is an index for prevention of astrocyte activation during ischemia. Thirty minutes before thoracic aorta occlusion, minocycline was administered for 18 minutes using a 2 F Fogarty catheter. Measurements and Main Results Minocycline given prophylactically significantly mitigated severe hindlimb motor impairment and reduced glial fibrillary acidic protein plus astrocytosis in both the white and gray matter of the spinal cord, caudal to the occlusion. Neuronal histologic cytoarchitecture, which was severely and significantly compromised in control animals, was preserved in the minocycline-treated animals. Conclusions This study's data imply that minocycline may attenuate reactive astrocytosis in response to injury with better neurologic outcome in a model of spinal cord ischemia in rats. The data suggest that future use of minocycline, clinically, might be advantageous in surgeries with a potential risk for paraplegia due to spinal cord ischemia.

Chest re-opening after cardiac surgery is performed in various instances, such as bleeding/tamponade, dehiscence of the sternum, or deep sternal wound infection. This chapter focuses on chest re-opening for bleeding/tamponade. Surgical site bleeding following cardiac surgery is not rare. Various methods for bleeding prevention are discussed, as well as diagnosis and indications for chest re-opening.

Anesthesia and intensive care, perioperative medicine and pain management, emergency medicine and resuscitation, all together constitute the field of action of the anesthesiologist. The definition of "anesthesiologist" underestimates the profession, and the lack of anesthesiologists seems understandable when we examine the scope of their activities throughout the hospital. There is little awareness among the public of the extent of the anesthesiologist's activity. The anesthesia segment itself, with all its importance, occupies a unique, yet modest part. The main activity of the anesthesiologist during surgery is reanimation, maintaining the patient in good shape while under anesthesia, and coping with hemodynamic changes that occur at every moment. The advantage of the anesthesiologist is that he is a "hospitalist," both the internal medical and surgical doctor. He must be profoundly skilled in all areas of medicine, CPR, pediatrics, women's medicine, general surgery, heart surgery, brain and orthopedic surgery, blood vessels, and many other fields. An important goal is to maintain our patients almost painless. Thus, early at the patient interview, the anesthesiologist will determine the course of the multi-modal analgesic management during hospitalization. Preemptive analgesic medication prior to surgical incision will reduce the pain that the patient will suffer after surgery. Whenever possible, the patient will receive a nerve blockage, or minute doses of opioids added to regional anesthetics. Pain management in the recovery room will be intensified by patient-controlled analgesia via infusion pumps, or by a wide variety of therapies, minimizing the use of oral opioid medications, thus avoiding addictive-prone behavior. This special issue of "Harefuah" is dedicated to anesthesia, pain management, and intensive care. The articles published in the current issue deal with key topics, such as fundamental changes occurring in resident education, emphasizing competent judgement and technical skills, and personal and caring approaches to the patient. The possibility that anesthesia may be associated with cognitive changes in infancy and in older age became a major concern and an active research field. Anesthetic complications can rapidly deteriorate and endanger the life of the patient, may leave him confused, and incapacitated. Larger and complicated modern surgeries are now possible thanks to the special skills and capabilities of the modern anesthesiologist to keep the patient alive and well, even in the presence of major surgery.

Objectives To identify the minocycline anti-inflammatory and antiapoptotic mechanisms through which it is believed to exert spinal cord protection during aortic occlusion in the rabbit model. Design An animal model of aortic occlusion-related spinal cord ischemia. Randomized study with a control group and pre-ischemia and post-ischemia escalating doses of minocycline to high-dose minocycline in the presence of either hyperglycemia, a pro-apoptotic maneuver, or wortmannin, a specific phosphatidylinositol 3-kinase antagonist. Setting Tertiary medical center and school of medicine laboratory. Participants Laboratory animals–rabbits. Interventions Balloon obstruction of infrarenal aorta introduced via femoral artery incision. Results Severe hindlimb paralysis (mean Tarlov score 0.36±0.81 out of 3) was observed in all the control group animals (9 of 11 with paraplegia and 2 of 11 with paraparesis) compared with 11 of 12 neurologically intact animals (mean Tarlov score 2.58±0.90 [p = 0.001 compared with control]) in the high-dose minocycline group. This protective effect was observed partially during a state of hyperglycemia and was completely abrogated by wortmannin. Minocycline administration resulted in higher neurologic scores (p = 0.003) and a shift to viable neurons and more apoptotic-stained nuclei resulting from reduced necrosis (p = 0.001). Conclusions In a rabbit model of infrarenal aortic occlusion, minocycline effectively reduced paraplegia by increasing the number of viable neurons in a dose-dependent manner. Its action was completely abrogated by inhibiting the phosphatidylinositol 3-kinase pathway and was inhibited partially by the pro-apoptotic hyperglycemia maneuver, indicating that the activation of cell salvage pathways and mitochondrial sites are possible targets of minocycline action in an ischemic spinal cord.

Sevoflurane postconditioning (sevo postC) is an attractive and amenable approach that can protect the myocardium against ischemia/reperfusion (I/R)-injury. Unlike ischemic preconditioning (IPC), sevo postC does not require additional induced ischemic periods to a heart that is already at risk. IPC was previously shown to generate myocardial protection against I/R-injury through regulation of iron homeostasis and de novo ferritin synthesis, a process found to be impaired in the diabetic state. The current study investigated whether alterations in iron homeostasis and ferritin mRNA and protein accumulation are also involved in the cardioprotective effects generated by sevo postC. It was also investigated whether the protective effects of sevo postC in the diabetic state can be salvaged by simvastatin, through inducing nitric oxide (NO) bioavailability/activity, in isolated streptozotocin (STZ)-induced diabetic hearts (DH). Isolated rat hearts from healthy Controls and diabetic animals were retrogradely perfused using the Langendorff configuration and subjected to prolonged ischemia and reperfusion, with and without (2.4 and 3.6%) sevo postC and/or pre-treatment with simvastatin (0.5 mg/kg). Sevo postC significantly reduced infarct size and improved myocardial function in healthy Controls but not in isolated DH. The sevo postC mediated myocardial protection against I/R-injury was not associated with de novo ferrtin synthesis. Furthermore, simvastatin aggravated myocardial injury after sevo postC in STZ-induced DHs, likely due to increasing NO levels. Despite the known mechanistic overlaps between PC and postC stimuli, distinct differences underlie the cardioprotective interventions against myocardial I/R-injury and are impaired in the DH. Sevo postC mediated cardioprotection, unlike IPC, does not involve de novo ferritin accumulation and cannot be rescued by simvastatin in STZ-induced DHs.

Preconditioning (PC) procedures (ischemic or pharmacological) are powerful procedures used for attaining protection against prolonged ischemia and reperfusion (I/R) injury, in a variety of organs, including the heart. The detailed molecular mechanisms underlying the protection by PC are however, complex and only partially understood. Recently, an ‘iron-based mechanism’ (IBM), that includes de novo ferritin synthesis and accumulation, was proposed to explain the specific steps in cardioprotection generated by IPC. The current study investigated whether nitric oxide (NO), generated by exogenous NO-donors, could play a role in the observed IBM of cardioprotection by IPC. Therefore, three distinct NO-donors were investigated at different concentrations (1–10 μM): sodium nitroprusside (SNP), 3-morpholinosydnonimine (SIN-1) and S-nitroso-N-acetylpenicillamine (SNAP). Isolated rat hearts were retrogradely perfused using the Langendorff configuration and subjected to prolonged ischemia and reperfusion with or without pretreatment by NO-donors. Hemodynamic parameters, infarct sizes and proteins of the methionine-centered redox cycle (MCRC) were analyzed, as well as cytosolic aconitase (CA) activity and ferritin protein levels. All NO-donors had significant effects on proteins involved in the MCRC system. Nonetheless, pretreatment with 10 μM SNAP was found to evoke the strongest effects on Msr activity, thioredoxin and thioredoxin reductase protein levels. These effects were accompanied with a significant reduction in infarct size, increased CA activity, and ferritin accumulation. Conversely, pretreatment with 2 μM SIN-1 increased infarct size and was associated with slightly lower ferritin protein levels. In conclusion, the abovementioned findings indicate that NO, depending on its bio-active redox form, can regulate iron metabolism and plays a role in the IBM of cardioprotection against reperfusion injury.

Background— Despite proven benefit in ambulatory patients with ischemic heart disease, the pattern of use of angiotensin-converting enzyme inhibitors (ACEIs) in coronary artery bypass graft surgery has been erratic and controversial. Methods and Results— This is a prospective observational study of 4224 patients undergoing coronary artery bypass graft surgery. The cohort included 1838 patients receiving ACEI therapy before surgery and 2386 (56.5%) without ACEI exposure. Postoperatively, the pattern of ACEI use yielded 4 groups: continuation, 915 (21.7%); withdrawal, 923 (21.8%); addition, 343 (8.1%); and no ACEI, 2043 (48.4%). Continuous treatment with ACEI versus no ACEI was associated with substantive reductions of risk of nonfatal events (adjusted odds ratio for the composite outcome, 0.69; 95% confidence interval, 0.52–0.91; P =0.009) and a cardiovascular event (odds ratio, 0.64; 95% confidence interval, 0.46–0.88; P =0.006). Addition of ACEI de novo postoperatively compared with no ACEI therapy was also associated with a significant reduction of risk of composite outcome (odds ratio, 0.56; 95% confidence interval, 0.38–0.84; P =0.004) and a cardiovascular event (odds ratio, 0.63; 95% confidence interval, 0.40–0.97; P =0.04). On the other hand, continuous treatment of ACEI versus withdrawal of ACEI was associated with decreased risk of the composite outcome (odds ratio, 0.50; 95% confidence interval, 0.38–0.66; P P P =0.005, respectively). No differences in in-hospital mortality and cerebral events were noted. Conclusions— Our study suggests that withdrawal of ACEI treatment after coronary artery bypass graft surgery is associated with nonfatal in-hospital ischemic events. Furthermore, continuation of ACEI or de novo ACEI therapy early after cardiac surgery is associated with improved in-hospital outcomes.

Background The possibility of restoring sevoflurane postconditioning (sevo-postC) cardioprotection in diabetic animals is uncertain. We hypothesized that attenuation of myocardial injury by sevo-postC might be hindered by inhibition of signal transducer and activator of transcription (STAT) 3-regulated activity of phosphatidylinositol 3-kinase (PI3K) in diabetic animals. To determine whether postC cardioprotection can be restored by normoglycemia, we treated rats with insulin. Methods Diabetic or nondiabetic rats were randomly subjected to 30-min ischemia/reperfusion, with ischemic postC or sevo-postC, with and without mitochondrial adenosine triphosphate-dependent potassium channel blocker 5-hydroxy decanoate sodium and PI3K antagonist wortmannin. The infarct area, phosphorylated STAT3, and apoptosis were examined. Studies were repeated after insulin treatment. Results Ischemic postC and sevo-postC significantly reduced infarct size by 50% in the nondiabetic rats (P < 0.002), a phenomenon completely reversed by 5-hydroxy decanoate sodium and wortmannin. Diabetes mellitus blocked the protective effect of postC, and insulin treatment to achieve normoglycemia did not restore cardioprotection. Phosphorylated STAT3 nuclear retention was significantly increased after ischemia-reperfusion and was further enhanced in response to ischemic postC (P < 0.05) but was significantly reduced in diabetic rats (by 43%; P < 0.01). Conclusions The effective reduction in infarct size and apoptosis in the nondiabetic rat heart by postC was completely abrogated in diabetic rats. This inhibition is not relieved by insulin-induced normoglycemia. The PI3K pathway and mitochondrial adenosine triphosphate-dependent potassium channel activation are involved in the mechanism of postC. In diabetic rats, STAT3 activation was strongly reduced, as was postC cardioprotection, suggesting that the inability of insulin to restore postC may be attributed to diabetes-induced STAT3-mediated inhibition of PI3K signaling.

Among ambulatory patients, an increase in pulse pressure (PP) is a well-established determinant of vascular risk. The relationship of PP and acute perioperative vascular outcome among patients having coronary artery bypass graft (CABG) surgery is less well known.We conducted a prospective observational study involving 5436 patients having elective CABG surgery requiring cardiopulmonary bypass. Of these, 4801 met final inclusion criteria. Comprehensive data were captured for medical history, intraoperative and postoperative physiologic and laboratory measures, diagnostic testing, and clinical events. The relationship between preoperative hypertension (systolic, diastolic, PP) and ischemic cardiac and cerebral outcomes and death was assessed using multivariable logistic regression; P0.05 was considered significant.Nine hundred and seventeen patients (19.1%) had fatal and nonfatal vascular complications, including 146 patients (3.0%) with cerebral and 715 patients (14.9%) with cardiac events. In-hospital mortality occurred in 147 patients (3.1%). Among all blood pressure variables measured preoperatively, PP was most strongly associated with an increased risk of postoperative complications. PP increments of 10 mm Hg (above a threshold of 40 mm Hg) were associated with an increased risk of cerebral events (adjusted odds ratio: 1.12; 95% CI [1.002-1.28]; P=0.026). The incidence of a cerebral event and/or death from neurologic complications nearly doubled for patients with PP80 mm Hg versusor=80 mm Hg (5.5% vs 2.8%; P=0.004). PP more than 80 mm Hg was also found to be associated with cardiac complications, increasing the incidence of congestive heart failure by 52%, and death from cardiac cause by nearly 100% (P=0.003 and 0.006, respectively).An increase in PP was independently and significantly associated with greater fatal and nonfatal adverse cerebral and cardiac outcomes in patients having CABG surgery. These findings highlight the associated risks of preoperative PP on acute postoperative vascular outcomes.

Reactive oxygen species are an important mediator in isoflurane-induced myocardial preconditioning. However, hydroxyl radicals are also released during reperfusion after regional ischaemia. The purpose of the present study was to test whether ischaemic preconditioning and isoflurane would influence the production of hydroxyl radicals during reperfusion.After i.v. administration of salicylate 100 mg kg(-1) and a 30 min stabilization period, New Zealand White rabbits were subjected to 40 min of regional myocardial ischaemia and 2 h of reperfusion. Ischaemic preconditioning was elicited by 5 min ischaemia followed by 10 min reperfusion (before the 40 min ischaemia). In another group, isoflurane (2.1%) was administered for 30 min, followed by 15 min washout, before the long ischaemia. Area at risk and infarct size were assessed by blue dye injection and tetrazolium chloride staining. We quantified the level of OH-mediated conversion of salicylate to its dihydrobenzoate derivatives (2,3- and 2,5-DHBAs). Normalized values of the DHBAs (ng DHBA per mg salicylate) were calculated.Mean (se) infarct size was 57 (6)% of the risk area in the untreated controls. This was significantly smaller in the ischaemic preconditioning and isoflurane groups: 22 (5) and 23 (6)% respectively. At 10 min of reperfusion, ischaemic preconditioning limited the mean increase in 2,3-DHBA to 24% from baseline, compared with 81% in control and 74% in the isoflurane group. Normalized 2,5-DHBA was maximally increased by 75% in the untreated group, 4 min after reperfusion. Ischaemic preconditioning significantly inhibited this increase (24% increase from baseline, P0.01). However, the increase observed in the isoflurane group was not different from control (71%).As already known, ischaemic preconditioning and isoflurane markedly reduced infarct size. However, only ischaemic preconditioning decreased postischaemic production of hydroxyl radicals. These different effects suggest different protective mechanisms at the cellular level.

The objective of this study was to assess the effects of ischemic preconditioning (IP) on hydroxyl free radical production in an in vivo rabbit model of regional ischemia and reperfusion. Another goal was to determine whether K(ATP) channels are involved in these effects. The hearts of anesthetized and mechanically ventilated New Zealand White rabbits were exposed through a left thoracotomy. After i.v. salicylate (100 mg/kg) administration, all animals underwent a 30-min stabilization period followed by 40 min of regional ischemia and 2 h of reperfusion. In the IP group, IP was elicited by 5 min of ischemia followed by 10 min of reperfusion (prior to the 40-min ischemia period). Glibenclamide, a K(ATP) channel blocker, was administered prior to the preconditioning stimulus. Infarct size was measured by 2,3,5-triphenyl tetrazolium chloride (TTC) staining. We quantified the hydroxyl-mediated conversion of salicylate to its 2,3 and 2,5-dihydroxybenzoate derivatives during reperfusion by high performance liquid chromatography coupled with electro-chemical detection.IP was evidenced by reduced infarct size compared to control animals: 22% vs. 58%, respectively. Glibenclamide inhibited this cardioprotective effect and infarct size was 53%. IP limited the increase in 2,3 and 2,5-dihydroxybenzoic acid to 24.3 and 23.8% above baseline, respectively. Glibenclamide abrogated this effect and the increase in 2,3 and 2,5-dihydroxybenzoic acid was 94.3 and 85% above baseline levels, respectively, similar to the increase in the control group. We demonstrated that IP decreased the formation of hydroxyl radicals during reperfusion. The fact that glibenclamide inhibited this effect, indicates that K(ATP) channels play a key role in this cardioprotective effect of IP.

Repair of descending thoracic and thoracoabdominal aortic aneurysms (TAAAs) is associated with a substantial risk of perioperative spinal cord ischemia that may or may not lead to permanent postoperative paralysis. Several techniques that aim to increase the ischemia tolerance time of the spinal cord during the period of aortic cross-clamping have been described in the literature.1 Hypothermia, left heart bypass, various shunts, myriad drugs, and cerebrospinal fluid (CSF) drainage have all been used alone or in combination to potentially improve neurologic outcome after surgery. CSF drainage and distal aortic perfusion have been shown to lower the incidence of neurologic complications after repair of type I and type II TAAAs. 2 Distal aortic perfusion increases distal aortic pressure, and CSF drainage decreases CSF pressure. These techniques potentially lead to an augmentation of spinal cord perfusion pressure during the period of aortic cross-clamping. However, CSF drainage can be associated with potentially serious complications, including fracture of the catheter during removal, catheter-associated meningitis, and/or temporary abducens nerve palsy, among others. 3 Also, epidural hematoma at the catheter insertion site can complicate the clinical assessment of postoperative spinal ischemic injury. 4 Intracranial subdural hematomas, with excessive CSF drainage, have also been reported and are associated with significant morbidity and mortality. 5 Subsequently, some authors have challenged the efficacy of CSF drainage and question the acceptable risk: benefit ratio of the technique. 6,7

Objective To examine the performance of a pediatric sedation team working according to a specific protocol and to assess parental satisfaction with the service. Study design A descriptive observational study of all procedures performed by the sedation team (comprising sedation-trained pediatric intensive care nurses and dedicated anesthesiologists) in a university hospital over 6 years. Data collected included demographics, procedure and location, sedation staff present, sedation failure, drugs used, requirements for escalation of sedation, complications, and parental satisfaction. Results Sedation was provided for 8760 procedures in 5554 children. The sedation nurse started 1769 (20%) procedures using triclofos sodium and required the assistance of the anesthesiologist in 115 (6.5%) cases. The remaining 6991 (80%) cases were performed by the anesthesiologist, predominantly using propofol (in 72.5% of cases). No cases were deferred as a result of insufficient sedation. Adverse events were recorded in 153 (1.7%) children. Of these, 132 (86%) were mild decreases in oxygen saturation. Three children were not discharged as a result of oversedation. Feedback indicated that 95% of parents were very satisfied with the sedation service. Conclusion A dedicated sedation team using a written protocol provides a service with minimal case cancellation, zero sedation failure, very good safety, and excellent parental satisfaction.

PURPOSE OF REVIEW This manuscript provides a critical review of the literature regarding the staffing of emergency medical services, with particular emphasis on anesthesiologists. RECENT FINDINGS Significant anesthesiology contributions to prehospital care include introduction of new airway management tools and improved physiological monitoring. Contributions to quality of care include patient benefit in terms of life years gained and a specific reduction in mortality from acute myocardial infarction. Intuitive concepts regarding the advantage of anesthesiologists in intubation mishaps and management of the failed airway have yet to be proven. Personnel limitations may be regional, necessitating local evaluation of anesthesiologist availability to staff ambulances. Since a major part of cost-effectiveness research is performed in the US where only paramedics staff ambulances, insufficient data exist regarding the financial implications of such practice. Burnout may be an important factor for deciding whether anesthesiologists should work in the operating room or ambulances or on an alternate basis. SUMMARY Further research should be performed to evaluate the clinical and financial implications of staffing ambulances with anesthesiologists or other physicians. Randomized controlled studies using standardized intubation techniques are necessary to examine whether prehospital airway management is improved when delivered by anesthesiologists.

OBJECTIVES The goal of this study was to investigate the nature of the association between silent ischemia and postoperative myocardial infarction (PMI). BACKGROUND Silent ischemia predicts cardiac morbidity and mortality in both ambulatory and postoperative patients. Whether silent stress-induced ischemia is merely a marker of extensive coronary artery disease or has a closer association with infarction has not been determined. METHODS In 185 consecutive patients undergoing vascular surgery, we correlated ischemia duration, as detected on a continuous 12-lead ST-trend monitoring during the period 48 h to 72 h after surgery, with cardiac troponin-I (cTn-I) measured in the first three postoperative days and with postoperative cardiac outcome. Postoperative myocardial infarction was defined as cTn-I >3.1 ng/ml accompanied by either typical symptoms or new ischemic electrocardiogram (ECG) findings. RESULTS During 11,132 patient-hours of monitoring, 38 patients (20.5%) had 66 transient ischemic events, all but one denoted by ST-segment depression. Twelve patients (6.5%) sustained PMI; one of those patients died. All infarctions were non-Q-wave and were detected by a rise in cTn-I during or immediately after prolonged, ST depression-type ischemia. The average duration of ischemia in patients with PMI was 226 ± 164 min (range: 29 to 625), compared with 38 ± 26 min (p = 0.0000) in 26 patients with ischemia but not infarction. Peak cTn-I strongly correlated with the longest, as well as cumulative, ischemia duration (r = 0.83 and r = 0.78, respectively). Ischemic ECG changes were completely reversible in all but one patient who had persistent new T wave inversion. All ischemic events culminating in PMI were preceded by an increase in heart rate (Δ heart rate = 32 ± 15 beats/min), and most (67%) of them began at the end of surgery and emergence from anesthesia. CONCLUSIONS Prolonged, ST depression-type ischemia progresses to MI and is strongly associated with the majority of cardiac complications after vascular surgery.

Patients having cataract surgery are usually elderly and have risk factors for ischemic heart disease. We sought to determine the incidence of perioperative myocardial ischemia in patients having cataract surgery and compare the influence of local anesthesia (LA) and general anesthesia (GA). Eighty-one patients undergoing cataract surgery with at least two risk factors for ischemic heart disease were monitored continuously for 24 h by using electrocardiogram leads II and V5 and a Holter recorder (Medilog 4500, Oxford Ltd, UK). Patients were randomly allocated to two groups, either LA (n = 39) or GA (n = 42). In the LA group, a peribulbar block was performed, whereas a similar block was performed in the GA group after tracheal intubation. The study demonstrated that cataract patients suffered from a frequent incidence of perioperative myocardial ischemia (31%). There was no difference in the incidence rate between the groups: 12 of 39 in the LA group and 13 of 42 in the GA group (P: = NS). However, the number of ischemic episodes was significantly increased in the GA group (18 vs. 13 in the LA group) (P0.05), and there were significantly more intraoperatively in the GA group (8 vs. 1) (P0.01). All intraoperative ischemic events were associated with tachycardia (or =20% of baseline), whereas postoperative ischemic changes were mostly independent of heart rate. Only one of the ischemic patients (in the GA group) was admitted as a result of intractable chest pain. There were significantly less intraoperative episodes in the LA group, suggesting that LA may be safer than GA in patients during this type of surgery.

Thoracotomy results in severe pain and deleterious changes in pulmonary physiology. These alterations are inevitable and can be minimized by effective analgesia. There are many options available for the treatment of postthoracotomy pain. Systemic opioids have been extensively used in this context but their side effects have led to the development of various routes of administration; the epidural route in combination with local anesthetics is the most effective. Other techniques include intercostal nerve block and intrapleural analge sia. Drugs such as clonidine, nonsteroidal anti-inflamma tory drugs, and ketamine are promising for the relief of pain after thoracotomy but further investigations are still warranted.

Retrograde cerebral perfusion through the superior vena cava (SVC) has been proposed to protect the brain from ischaemic injury during profound hypothermic circulatory arrest (PHCA). Its contribution to cerebral protection is unclear. Furthermore, the addition of anaesthetic or vasodilating agents to the SVC perfusate to enhance brain protection, has never been described.In three patients undergoing repair of the ascending aorta utilizing PHCA, the upper body was retrogradely perfused with cold (16 degrees C) blood through the SVC by the cardiopulmonary bypass pump. Electroencephalographic activity was monitored using a computerized electroencephalographic monitor (Cerebro Trac 2500, SRD). Perfusion pressure was measured at a port in the cannula connector. Etomidate or thiopentone was injected into the SVC perfusate to arrest reappearing electroencephalographic activity. Nitroglycerin or nitroprusside was injected into the perfusate to increase retrograde flow and maintain a constant perfusion pressure.During PHCA periods of up to 61 min, recurrent electroencephalographic activity was abolished by the retrograde administration of small boluses of etomidate (total 50 mg) or thiopentone (total 500 mg). Nitroprusside (100 micrograms) and nitroglycerin (2 micrograms.kg-1.min-1) increased retrograde flow from 220 to 550 and 660 ml.min-1, respectively, while maintaining perfusion pressure (25-26 mmHg). Recovery from anaesthesia and surgery was uneventful, with no adverse neurological sequelae.Injection of anaesthetic agents into the retrograde SVC perfusate during PHCA, can suppress reoccurring electroencephalographic activity and retrograde injection of vasodilators can facilitate an increase in perfusion. It is suggested that both may augment brain protection.

Background Although ischemic injury to the spinal cord is a well-known complication of aortic surgery, no metabolic markers have been identified as predictors of an adverse outcome. This study evaluated the effect of cerebrospinal fluid (CSF) drainage, with and without distal femoral perfusion or moderate hypothermia on blood and CSF lactate concentrations and CSF pressure during thoracoabdominal aortic aneurysm surgery. Methods Three nonconcurrent groups of patients were studied prospectively: patients with normal body temperature (35 degrees C) but without distal femoral bypass (n = 6), patients with normal body temperature with bypass (n = 7), and patients with hypothermia (30 degrees C) and bypass (n = 8). In all patients, CSF pressure was recorded before, during, and after aortic cross-clamping. During the surgical repair, CSF drainage was performed using a 4-Fr intrathecal silicone catheter. Blood and CSF lactate concentrations were measured throughout the operation. Results Significant increases in blood (490%) and CSF (173%) lactate concentrations were observed during and after thoracic aortic occlusion in patients with normothermia and no bypass (P < 0.02 and 0.05, respectively). Distal perfusion attenuated the increase in both blood and CSF lactate (P < 0.01), and a further reduction was achieved with hypothermia of 30 degrees C (P < 0.001). Patients who became paraplegic showed a greater increase in CSF lactate concentrations after aortic clamp release compared with those who suffered no neurological damage (275% vs. 123% of baseline; P < 0.05). Increased CSF pressure of 42-60% (P < 0.005) was noted soon after thoracic aortic occlusion, both with and without distal femoral bypass. Conclusions Incremental reductions in CSF lactate concentrations were achieved using distal femoral bypass and hypothermia. The reduction in CSF lactate correlated with the methods used to protect the spinal cord during thoracoabdominal aortic aneurysm surgery and was associated with better outcome. Decompression by distal bypass of the hemodynamic overload caused by aortic occlusion was insufficient to eliminate the acute increase in CSF pressure. Cerebrospinal fluid lactate measurements during high aortic surgery may accurately represent the spinal cord metabolic balance.

The purpose of this study was to compare transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) in the evaluation of the coronary sinus and its blood flow. Forty patients were studied by TTE and TEE. The distal coronary sinus and its right atrial communication could be identified in 21 of 40 by TTE, and in all patients by TEE. Coronary sinus diameter measurement at the right atrial communication was possible by TTE in 16 of 40, and in all patients by TEE (maximal diameter 6 to 14 mm, mean 9 +/- 2). Flow velocity measurement by pulsed Doppler was possible in 25 of 40 patients (63%) by TEE, and in none by TTE. The flow velocity pattern was similar to central vein flow velocity, with systolic and diastolic antegrade waves, and a small retrograde end diastolic wave. The coronary sinus cross-sectional area was measured in 5 patients by intravascular ultrasound. It varied in size and shape during the cardiac cycle, reaching a maximum (0.3 to 1.5 cm2) at end diastole, and decreasing by 40% to 70% at end systole. TEE is superior to TTE in the evaluation of the coronary sinus and its blood flow velocity. However, because of the variability in cross-sectional area size and shape, measurement of coronary sinus blood flow may be inaccurate.

Repair of a thoracoabdominal aneurysm involves a significant risk of ischemic injury to the spinal cord. Standard monitoring of somatosensory evoked potentials, which relies upon peripheral nerve stimulation, becomes nonspecific and insensitive during this surgery when aortic cross-clamping produces lower extremity ischemia causing a peripheral conduction block. Techniques for the insertion of percutaneous epidural electrodes, developed originally for pain management, have been adapted to this setting to permit direct stimulation of the spinal cord for intraoperative monitoring of evoked potentials. The clinical outcome in patients monitored by this technique has been consistent with evoked potential findings.

Forty-seven patients underwent selective catherization of middle and lower thoracic intercostal and upper lumbar arteries to define the origin of the artery of Adamkiewicz. One patient had significant atheroembolism, and a second had transient lower extremity paresthesias. No other complications occurred. The origin was found in 26 (55%), and 21 patients underwent thoracoabdominal aneurysm repair with this knowledge. When the critical lumbar or intercostal artery could be included as part of a long proximal or distal anastomosis, all 12 patients could be included as part of a long proximal or distal anastomosis, all 12 patients survived, and one was paralyzed. However, if the aneurysm repair mandated a midgraft anastomosis to intercostal arteries critical to spinal cord perfusion, seven of nine patients either died or were paralyzed (p < 0.05). In the group of 19 patients operated on in whom spinal cord blood supply was not identified three patients had a technically unsuccessful operation; two died, and one was paralyzed. Twelve of 16 patients who had an adequate, but unsuccessful attempt at localization were treated by intercostal “neglect” and survived. Late paresis developed in two patients, but they are walking now. One of the patients who died had multiple systems failure and awakened paraplegic. She had a patent, enlarged, thoracic radicular artery at T-5 which probably supplied to spinal cord and which was missed angiographically. Paralysis was associated with aneurysm extent (group 2 and III B, dissections vs group 1 & 3, p < 0.05). Selective intercostal angiography requires further refinement, but it is safe and offers the promise of understanding the mechanisms and risks of spinal cord complications after repair of extensive thoracoabdominal aneurysms. (J VASC SURG 1991;13:23-35.)

A 63-year-old woman with metastatic breast cancer was referred to our bronchoscopy unit for outpatient laser resection of an endobronchial mass through fiberoptic bronchoscopy. The patient had no history of ischemic heart disease. During the procedure, the patient developed an ST-segment elevation and a complete atrioventricular block. IV nitroglycerin and morphine were effective in treating this episode. In this patient, we were able to demonstrate a focal spasm by postbronchoscopy coronary angiography.

During off-pump coronary artery bypass (OPCAB) surgery, the heart is subjected to ischemia and reperfusion. The authors hypothesized that the volatile anesthetics are as effective as ischemic preconditioning (IPC) in preserving myocardial function during off-pump cardiac surgery, and this effect is because of multiple mechanisms of action. Therefore, the effects of enflurane with its calcium inhibition and antioxidative properties were compared with mechanical IPC in preserving myocardial cellular markers.A prospective, randomized, controlled, and partly blinded study.A tertiary care university hospital.Twenty-five patients undergoing elective single-graft OPCAB surgery.Patients were randomized into 3 groups: (1) control (n = 8), (2) a single 5-minute ischemia/reperfusion interval of IPC before coronary occlusion (n = 9), and (3) 1.6% enflurane anesthesia 15 minutes before and during graft attachment (n = 8). Arterial and coronary sinus venous blood were analyzed for biochemical indices of ischemia and hydroxyl radical generation.Although the hemodynamic changes were small, myocardial lactate production in the control group increased by 120%, whereas in the enflurane group it decreased significantly (p0.01) compared with the control and IPC groups. Oxygen utilization in the control group was 44% higher (p0.03), and there was also a larger release of the hydroxyl radical-dependent adduct 2,3-dihydroxybenzoic acid (225% increase, p0.05) compared with both study groups. During reperfusion, initial anterior wall hypokinesis by TEE was observed, with slow recovery during reperfusion compared with early recovery in both study groups.Coronary occlusion during OPCAB surgery results in increased production of ischemia-related metabolic products. The application of methods such as IPC or volatile anesthesia appears to reduce the metabolic deficit, free-radical production, and physiologic changes.

PURPOSE OF REVIEW With this article we intend to increase the awareness of the efficiency and efficacy of peripheral nerve block as a treatment option for outpatient surgical anesthesia and postoperative home-based analgesia. RECENT FINDINGS Current investigations have demonstrated that peripheral nerve block is associated with a superior outcome (reduced pain, nausea and vomiting) and more efficient patient turnover than general anesthesia. Continuous peripheral nerve block and patient controlled peripheral nerve block lead to further improvement in postoperative analgesia and patient satisfaction. SUMMARY The recent advances and techniques described indicate that peripheral nerve block is both a valid and frequently a preferred option for ambulatory surgery.

Background The goal of the current study was to assess the effects of flumazenil, a benzodiazepine receptor antagonist, in limiting infarct size and in reducing hydroxyl free radical production. Methods After intravenous salicylate (100 mg/kg) administration, rabbits were subjected to 40 min of regional myocardial ischemia and 2 h of reperfusion. In one group, flumazenil (0.05 mg/kg) and, in another, midazolam (0.05 mg/kg) was administered 15 min before 40 min of ischemia. Ischemic preconditioning (IP) was elicited by 5 min of ischemia followed by 10 min of reperfusion (before the 40-min ischemia period). In two other groups, midazolam was added to flumazenil and IP. Infarct size was determined using triphenyl tetrazolium chloride staining. The authors quantified the hydroxyl-mediated conversion of salicylate to its 2,3- and 2,5-dihydroxybenzoate derivatives during reperfusion by high-performance liquid chromatography coupled with electrochemical detection. Results are expressed as mean +/- SEM. Results Flumazenil, like IP, significantly decreased infarct size (23 +/- 4 and 22 +/- 5%, respectively, vs. 57 +/- 6% in control group; P < 0.01). Midazolam inhibited the effects of flumazenil and IP. Flumazenil and IP significantly limited the increase in the normalized concentrations of 2,3- and 2,5-dihydroxybenzoic acids. With midazolam, however, the increase was comparable to that of the control group. 5-Hydroxydecanoate, a selective mitochondrial adenosine triphosphate-sensitive K channel blocker, given with flumazenil, abolished the protection obtained with the latter. Conclusions Flumazenil mimics preconditioning to decrease infarct size and hydroxyl radical production during reperfusion. Midazolam, however, abolishes these effects. Blockade of benzodiazepine receptors is upstream to the mitochondrial adenosine triphosphate-sensitive K channels in the preconditioning cascade.

Anticoagulation for cardiopulmonary bypass in patients with heparin-induced thrombocytopenia requires the use of other anticoagulants. We report a case in whom this was achieved using the heparinoid danaparoid (Orgaran). Based on our experience and a review of the literature, we provide guidelines for managing these rare patients. A danaparoid dose substantially lower than that recommended by the manufacturer may minimize bleeding complications.

Background and objective: Isoflurane has been shown to mimic ischaemic preconditioning (IPC). The protective effect of IPC, or applying isoflurane or perfusion with the 'push-pull' complex zinc-desferrioxamine (Zn-DFO) in the canine heart, was investigated. Methods: Thirty minutes after salicylate administration (100 mg kg - 1 ) the heart was exposed. All dogs were subjected to a 10 min left anterior descending artery qcclusion followed by 2 h of reperfusion. In Group I (n = 9) isoflurane (2.5%) was administered 10 min prior to and during ischaemia. In Group II (n = 8), IPC was elicited by 5 min coronary artery occlusion, followed by 5 min of reperfusion, prior to the 10 min ischaemia. In Group III (n = 9) Zn-DFO (2.5 mg kg - 1 ) was given 10 min prior to ischaemia. The effects of these interventions were compared to control (n = 10). Coronary sinus blood concentrations of salicylate, 2,3-dihydroxybenzoic acid (DHBA), lactate, pH and oxygen content were monitored. Results: In the control group, 2,3-DHBA increased by 32% above the pre-ischaemic value (P < 0.05). In contrast, in the IPC hearts, a significant decrease in the production of 2,3-DHBA was observed (40% lower than baseline, P < 0.01). In the isoflurane group only a 13% (and non-significant) decrease was noticed. In the Zn-DFO group a 33% decrease was found (P < 0.01). The increase in lactate concentrations in the IPC and Zn-DFO groups was significantly smaller than that of control and isoflurane groups. Conclusions: IPC protected the heart against the deleterious effects of reperfusion, possibly by amelioration of the level of oxygen-derived reactive species, and the complete inhibition of reactive hydroxyl radical production. Isoflurane did not prove to be as effective in reducing the free radical damage.

Summary Thoracic epidural analgesia can effectively relieve post-thoracotomy pain but may also adversely affect pulmonary function. This randomised, prospective study compared the effects on pulmonary function of three different epidural analgesics (clonidine, bupivacaine and methadone). Forty-seven patients undergoing thoracotomy were treated postoperatively for 72 h with one of the study drugs. Doses were titrated to maintain visual analogue pain scale values below 4 out of 10. Throughout the postoperative period, reductions of up to 70% of the pre-operative value were observed in forced expiratory volume in 1 s, forced vital capacity and peak expiratory flow rate. Patients who received clonidine showed significantly faster recovery rates of forced expiratory variables compared to other patients, and by the third postoperative day significantly higher spirometry values (10–15%) were recorded in this group. As clonidine was the most effective drug in terms of preservation of pre-operative lung function, it may be clinically advantageous in post-thoracotomy patients.

Objective: To evaluate the time course of neuromuscular blockade after rocuronium in children with intracardiac shunts. Design: Prospective study. Setting: University hospital. Participants: Consecutive children (n = 52) with intracardiac shunts scheduled for elective cardiac surgery. Participants were allocated to 2 groups according to the direction of the shunt. Interventions: Rocuronium, 0.6 mg/kg, was administered for muscle relaxation. The ulnar nerve was stimulated at 20-second intervals with a supramaximal 2-Hz train-of-4 stimulation (TOF-Guard nerve stimulator; Biomet International, Odense, Denmark). The onset time to maximal twitch depression and the time to clinical recovery were compared between the 2 groups. Measurements and Main Results: The time to maximal block was significantly faster in children with a right-to-left shunt: 56.8 ± 5.3 seconds versus 77.1 ± 6.6 seconds (p = 0.01). There was a tendency to shorter recovery in children with a right-to-left shunt: 42.3 ± 6.1 minutes versus 55.4 ± 4.9 minutes (p = NS). Conclusion: This study shows a more rapid onset of rocuronium in children with cyanotic congenital heart disease. In these patients, rocuronium is indicated, particularly for rapid airway control. Copyright 2002, Elsevier Science (USA). All rights reserved.

To describe the perioperative cardiac morbidity in adult patients undergoing retinal surgery using continuous Holter monitoring.Prospective study.University hospital.56 patients scheduled for elective retinal surgery with local anesthesia.Patients were monitored continuously for 24 hours using a Holter recorder. Blood samples for creatine phosphokinase (CPK) and serum myocardial creatine phosphokinase (CPK-MB) were taken preoperatively and 24 hours postoperatively. The characteristics of myocardial ischemia were compared according to the number of risk factors for ischemic heart disease.The overall incidence of perioperative myocardial ischemia was high: 26.7% (n = 15). These patients exhibited 41 episodes of ischemia with mean ST segment change from baseline of 2.2+/-0.7 mm. However, almost all (93.3%) ischemic episodes were silent. Patients with two risk factors or more had 77% more episodes of ischemia than patients with one risk factor (p0.005), and the duration of ischemia was 47+/-22.5 minutes compared with 34.8+/-27.5 minutes (p = NS). The first episode of ischemia occurred an average of 10 hours after surgery. No patient had intraoperative evidence of ischemia. Half of the ischemic episodes were associated with an increase in heart rate. No patient had evidence of acute myocardial infarction.Retinal surgery with local anesthesia is accompanied by a high incidence of postoperative myocardial ischemia. No negative outcome was correlated to the occurrence of postoperative myocardial ischemia. The significance of these findings has yet to be evaluated.

Study Objective: To evaluate systolic pressure variation (SPV), defined as the difference between the maximum and minimum systolic blood pressure measured during a controlled mechanical respiratory cycle, as a predictor of the cardiac output (CO) response to an acute decrease in ventricular preload. Design: Prospective study with each subject serving as his or her own control. Setting: Cardiac surgery operating rooms of a university medical center. Patients: 15 adults with good ventricular function undergoing coronary artery bypass grafting. Intervention: During stable anesthetic conditions and before surgical stimulation, 500 ml of blood was removed from each patient over 10 minutes. Measurements and Main Results: CO, central venous pressure (CVP), pulmonary artery diastolic pressure, and pulmonary artery occlusion pressure (PAOP), and SPV before and after phlebotomy were recorded. Phlebotomy was associated with significant decreases in CVP, PAOP, and CO, and an increase in SPV. Of these variables, SPV was the best predictor of the percent decrease in CO resulting from blood loss. Conclusion: SPV is a dynamic measurement, which, by revealing the response to small cyclical changes in left ventricular preload that occur during the controlled mechanical respiratory cycle, is a better predictor than central filling pressures of the response of CO to acute decreases in preload that occur as a result of acute blood loss.

Study objective To study the incidence of myocardial ischemia and related hemodynamic alterations in sedated patients undergoing fiberoptic bronchoscopy (FOB). Design Prospective study. Setting Tertiary care, university hospital. Patients Twenty-nine patients, age 50 years or older, undergoing elective FOB. Interventions Myocardial ischemia was assessed by continuous ECG monitoring beginning 30 min before, and until 2 h after FOB. Measurements and results During FOB, there was a significant rise in heart rate (89±3 [mean±SE] to 120±4 beats/min) and fall in oxygen saturation (95±1 to 90±1%). There was no significant rise in systolic or diastolic BP. Five patients (17%) had myocardial ischemia during FOB that lasted 20±8 min. Their demographic and pre-FOB characteristics were not different from the other patients. Compared to baseline values, a significant rise in heart rate, a fall in oxygen saturation, and no significant change in BP were observed during FOB in patients, both with or without ischemia. Although not statistically significant, ischemia was associated with more protracted procedures. Conclusions Myocardial ischemia may develop in elderly patients undergoing FOB. This observation encourages the routine use of ECG and oximetry during FOB, allowing for early intervention to prevent the dangerous combination of hypoxia, tachycardia, and myocardial ischemia. Moreover, this study suggests that methods to ensure oxygenation during FOB should be adhered to, and that the routine administration of atropine should be reconsidered.

Background Recent studies indicate that during regional myocardial ischemia and subsequent reperfusion, volatile anesthetics may provide protection against free radical-related injury. The effect of halothane on free radical production during ischemia and reperfusion, in the canine heart, was investigated. The level of hydroxyl radical (.OH)-mediated conversion of salicylate to its dehydroxybenzoate derivatives (2,3-DHBA and 2,5-DHBA) was monitored. Methods Under general anesthesia, the heart was exposed through median sternotomy. Salicylate (100 mg/kg given intravenously) was administered 30 min before left anterior descending artery occlusion. Six dogs were studied using inhaled halothane (1.6%) 10 min before and during the 10-min ischemic period, followed by 50 min of reperfusion, and then they were compared with seven other dogs used as controls. Blood concentrations of salicylate, 2,3-DHBA and 2,5-DHBA, K+, lactate, oxygen content, and pH were monitored. Results An acute increase in the normalized concentrations of 2,3-DHBA and 2,5-DHBA was observed in the control animals during reperfusion. In contrast, halothane inhalation completely inhibited the production of both metabolites (P < 0.02), but 2,5-DHBA concentrations in the halothane-treated group were even less than the basal level (P < 0.05). The increase in lactate concentrations in the experimental animals was significantly less than that of controls (P < 0.05) and followed the same time-dependent pattern as the changes in K+ and pH. Halothane significantly decreased (P < 0.0001) the difference in oxygen content between coronary sinus and aortic root blood, suggesting decreased oxygen utilization during reperfusion. Conclusions Halothane completely inhibited the production of .OH, and its administration may protect the heart from the deleterious effect of oxygen-derived reactive species, with attenuation of the metabolic response to ischemia.

Background Myocardial protection during open heart surgery is based on administration of oxygenated blood cardioplegia, the preferred temperature of which is still under debate. The current randomized study was designed to prospectively evaluate the quality of myocardial protection and the functional recovery of the heart with either normothermic (group N) or hypothermic (group H) oxygenated blood cardioplegia. Methods Under continuous electrocardiographic Holter monitoring, 42 patients were randomly scheduled to receive either normothermic (33.5 degrees C) or hypothermic (10 degrees C) cardioplegia solutions during coronary bypass grafting surgery. Blood samples for creatinine phosphokinase, creatinine phosphokinase-MB, lactate, epinephrine, and norepinephrine were withdrawn during cardiopulmonary bypass via a coronary sinus cannula. Results Active cooling in group H on initiation of cardiopulmonary bypass was characterized by transition through ventricular fibrillation in 75% of patients, whereas in group N atrial fibrillation occurred in 65% of patients. On myocardial reperfusion, sinus rhythm spontaneously resumed in 95% of group N patients compared to 25% in group H (P = 0.0003). In the latter, 75% of patients developed ventricular fibrillation often followed by complete atrioventricular block, which necessitated temporary pacing for a mean duration of 168 +/- 32 min. Both groups showed a similar incidence of intraventricular block and ST segment changes. However, the incidence of ventricular premature beats in the first 16 h after cardiopulmonary bypass was significantly greater in group H (P < 0.05), 20 +/- 26/h, compared to 3 +/- 5/h in group N. Blood concentrations of lactate, creatinine phosphokinase, epinephrine, and norepinephrine increased gradually during the operation, but the differences between the groups were not significant. Conclusions The current prospective human study suggests that the increased susceptibility for ventricular fibrillation and dysrhythmia, and the delayed recovery of the conduction system after hypothermic myocardial protection, are related to temperature-induced changes in vital cellular functions of the conduction tissue in the postischemic period. Both cardioplegic methods provide adequate myocardial protection but normothermic oxygenated blood cardioplegia may accelerate recovery of the heart after cardiopulmonary bypass.

The purpose of this review is to define the expectations of an on-line automatic patient data management system (PDMS) into anaesthesia work-stations in and around the operating room suite. These expectations are based on review of available information in the medical literature, and trials of several systems that are available commercially, three of them in a more detailed fashion (i.e. Informatics, Datex and North American Drager). The ideal PDMS should: -- communicate with and capture the information from different monitors, anaesthesia machines and electronic gadgets (e.g., infusion pumps) used in the operating room (OR), while presenting selected relevant values and trends on a screen. -- inform the anaesthetist of deviations from preselected limits of physiological and technical values. In the future, the system will hopefully be upgraded to include an algorithm-based decision support system. -- communicate with the hospital mainframe computer, and automatically transfer demographic data, laboratory and imaging results, and records obtained during preoperative consultations. -- at the end of each anaesthetic procedure, create an anaesthetic record with relevant data automatically collected by the system, as well as that which was entered manually by the physician during the procedure. A copy of this anaesthesia file must be kept on a computerized archive system. None of the systems so far evaluated fulfilled all our expectations. We have therefore adopted approach for the gradual introduction of such a system into our OR environment over the next two to five years, during which expected improvements may be incorporated to upgrade the system.

BACKGROUND Recent experimental data suggest that functional and metabolic changes in the myocardium caused during ischemia and subsequent reperfusion may be attenuated by the volatile anesthetics through the prevention of intracellular calcium accumulation. The main purpose of the current research is to identify a mechanism responsible for the alterations of ischemia-associated injury to the voltage-sensitive Ca2+ channels (VSCC) in the sarcolemma during halothane anesthesia. METHODS The effect of 10 min myocardial ischemia in canine heart and 20 min reperfusion on the function of the VSCC in the sarcolemma was examined in the presence or absence of 1.6 vol% halothane administered in vivo. The membranes were isolated through differential centrifugation/filtration from the ischemic (left anterior descending territory) and normally perfused myocardium. Comparison of binding characteristics in the ischemic and nonischemic zones was made using equilibrium-binding studies of a dihydropyridine calcium channel blocker, [3H]isradipine (0.05-1.0 nM), to the VSCC in the sarcolemma. Control studies were performed on membranes prepared from the same perfusion zones, but from hearts who were not exposed to ischemia. RESULTS The control studies (n = 5) showed no difference in binding kinetics between the different zones in the heart. After 10 min of ischemia, a 50 to 95% increase in specific [3H]isradipine binding to the sarcolemmal membranes was observed as compared to control membranes (P < 0.001). The maximal binding capacity (Bmax) increased by 85%, whereas the dissociation constant (Kd) remained unchanged. In the reperfusion experiments, a moderately increased binding (of 32%) was observed with a 40% increase in Bmax (P = NS). In the presence of 1.6% inhaled halothane, the effect of ischemia was attenuated. A decrease of 32.1% to 41.8% in equilibrium binding was observed (31% decrease in Bmax; P < 0.03 and 0.02, respectively). CONCLUSIONS Even a brief period of myocardial ischemia produces a marked increase in the available high-affinity binding sites in the VSCC, a finding that is well correlated with previous experimental observation of increased calcium ion influx to the myocardial cell. On reperfusion, some recovery of the ischemic changes in the VSCC was evident. The binding kinetics which characterize this early phase of cell injury were reversed by halothane anesthesia, indicating a possible reduction in calcium entry, which may represent one of the beneficial effects of the anesthetic in the ischemic heart.

Publisher Summary In this chapter, the effect of a short period of ischemia and reperfusion on the voltage-sensitive calcium channels (VSCC) has been evaluated. Equilibrium binding studies of the dihydropyridine calcium channel blocker [ 3 H] isradipine have been used to evaluate the influence of ischemia and reperfusion on the VSCC, as well as the ischemia effect in the presence or absence of halothane anesthesia. Isradipine binds to the VSCC in a specific, saturable, and reversible manner, and it can be used as a probe of these channels. Three control studies have been performed to evaluate the binding capacity of [ 3 H]isradipine to different areas of the ventricular muscle. These studies have showed that halothane inhibits the Ca 2+ accumulation associated with myocardial ischemia in isolated guinea pig hearts, demonstrating a potentially beneficial effect of the anesthetic on the ischemic heart. The role of halothane in preventing ischemia-induced dysrhythmias and attenuation of free radical generation on reperfusion offers a new potential use during open heart surgery. The method of continuous perfusion of oxygenated blood cardioplegia, retrogradely, through the coronary sinus, enables a concomitant administration of the volatile anesthetics (VA) before and during the ischemic period of the cardiopulmonary bypass. There is a scope for further studies that may promote the use of the volatile anesthetic when myocardial ischemia and reperfusion are present during open heart surgery.

The effect of intrathecal (IT) administration of three different doses (1, 2.5, and 5 micrograms/kg) of alfentanil on lower urinary tract dynamics was examined by urodynamic studies, cystometrograms (CMG), and urethral pressure profiles (UPP) in seven anesthetized dogs. Simultaneous serum drug concentrations were determined by specific radioimmunoassay for time-response analysis. A significant dose-dependent relaxation of urethral musculature expressed by a reduction in UPP values of 41.5% and 38.4% (P < 0.03) was noted 30 min after 5 and 2.5 micrograms/kg IT alfentanil, respectively, whereas the decrease of 13.4-22% in mean CMG values was not significant. All changes in UPP and CMG returned to baseline values by 60 min. The pharmacokinetics of alfentanil from the cerebrospinal fluid to the systemic circulation were linear, i.e., dose-independent with maximal serum concentrations of 0.6, 1.4, and 3.5 ng/mL 10 min after the three respective IT doses. The low serum alfentanil concentrations and the lack of time correlation between the peak values and the changes in urinary tract activity, point to a spinally mediated mechanism. The short-lived effect of IT alfentanil on lower urinary tract dynamics and the relaxation of the bladder neck allow for unobstructed micturition pathways and may avoid urinary retention.

Although monitoring of somatosensory evoked potentials elicited from stimulation of lower extremity peripheral nerves has been suggested as a method for assessing neural function during thoracoabdominal aortic aneurysm surgery, this technique has been reported to yield a large number of false positives. It was believed that direct stimulation of the spinal cord would eliminate some of the problems associated with peripheral evoked potentials. The present study compared in 18 patients the use of scalp recorded evoked potential following stimulation of either the posterior tibial nerve via percutaneous needles or the spinal cord via an epidural electrode previously placed fluoroscopically. In 10 patients in whom distal bypass or shunt was not used, peripheral evoked potentials totally disappeared within 5-30 min of aortic clamping. Spinal cord stimulation evoked potentials disappeared permanently in 2 patients shortly after aortic cross-clamping; 1 died shortly after the procedure, and the other awoke densely paraplegic and died the next day. When distal perfusion was maintained by shunt or bypass, the disappearance of both peripheral and spinal evoked potentials accurately predicted the neurologic outcome of 1 paralyzed patient. Loss of spinal cord stimulation evoked potentials was found to be correlated with adverse neurologic outcome. Over the period of aortic clamping a gradual decrease in mean amplitude (50% at 45 min [P less than 0.05]) and a 20% increase in mean latency time were observed. Maintenance of adequate distal perfusion may permit the use of peripheral evoked potentials in the assessment of spinal cord ischemia during aortic cross-clamping.(ABSTRACT TRUNCATED AT 250 WORDS)

Several pieces of evidence exist which suggest that the volatile anesthetics exert their negative inotropic effect by interfering with the calcium homeostasis of the myocardial cell.1 Our laboratory has examined three important sites in the myocardial cell that are known to be involved with the phasic changes in intracellular calcium which occur during contraction. These sites are the sarcolemma, the sarcoplasmic reticulum, and the myofibrils. This paper is directed towards our investigations of one constituent of the sarcolemma, the voltage-dependent calcium channel (VDCC), and its probable alteration by the volatile anesthetic, halothane.

Volatile anesthetics produce their negative inotropic effect on the heart mainly by interference with calcium homeostasis in the myocardial cell. In order to elucidate the mechanism of the depression, we have evaluated the effect of the volatile anesthetics on the binding of the calcium channel blocker [3H]nitrendipine to purified bovine cardiac sarcolemma. The radioligand binding studies were carried out at 25 degrees C, with increasing concentrations of [3H]nitrendipine (0.01-1 nM), in the presence or absence of unlabeled nitrendipine to determine specific binding, and with or without 1.9% halothane, 2.3% isoflurane, and 4.8% enflurane. Separately, [3H]nitrendipine was measured in the presence of increasing doses of halothane (0.78, 1.33, 1.90, and 2.57%). Kinetic studies of association and dissociation rate were performed with 1.90% halothane and 1 nM [3H]nitrendipine at different time intervals. All three volatile anesthetics produced depression of [3H]nitrendipine binding to the isolated cardiac sarcolemma. Only halothane produced a significant depression in binding, ranging between 59 and 66% (P less than 0.05), depending on the concentration of [3H]nitrendipine used. Isoflurane produced 29-38% depression, and enflurane produced 5-22% depression. Halothane also produced a significant (P less than 0.01) dose-dependent decrease in [3H]nitrendipine-specific binding. The kinetic binding experiments demonstrated that the time course for halothane's effect on association and dissociation of [3H]nitrendipine was 5 min for the half-maximum effect; the maximal reduction in binding capacity was at 15-30 min (P less than 0.05). Scatchard analysis revealed that all three volatile anesthetics produced reduction in the maximal number of binding sites; however, they varied in their effect on binding affinity. Only halothane produced a homogenous increase in the dissociation constant, signifying reduced affinity of the Ca2+ blocker to the channel. We suggest that the volatile anesthetics produce conformational changes in these channels consistent with their ability to depress channel-mediated Ca2+ influx into myocytes.