Prevention of perioperative venous thromboembolism and coronary events: differential responsiveness to an intervention program to improve guidelines adherence.

INTRODUCTION: Prevention of venous thromboembolism and coronary events (with beta-blockers) during and after surgery is at the top of a list of safety practices for hospitalized patients, recommended by the Agency for Health Care Research and Quality (AHRQ). We wished to determine and improve adherence to clinical guidelines for these topics in our institution. PATIENTS, MATERIAL, AND METHODS: A prospective survey was conducted over several weeks on operated patients in a 1200-beds medical center (a teaching, community and referral hospital in Jerusalem, Israel). Eligibility for and actual administration of prophylactic treatment with anticoagulant and beta-blockers were determined. Following an intervention program, which included staff meetings, development of local protocols, and academic detailing by a nurse, the survey was repeated. RESULTS: In general, adherence to recommended anticoagulation prophylaxis was low, found in only 29% [95% confidence interval (CI) = 23-36] of eligible patients. After the intervention, adequate anticoagulation increased to 50% (95% CI = 40-59) of eligible patients (P < 0.001). Initiation of beta-blockers in preventing perioperative cardiac events was very low (0%, 95% CI = 0-5%) and did not increase after intervention. CONCLUSIONS: Adherence to guidelines for prevention of surgical complications was found to be low in our institution. A multifaceted intervention significantly increased use of prophylaxis for venous thromboembolism but not for coronary events. This differential response suggests that the success of a quality improvement project strongly depends on topic content and its phase of acceptance.

Isoflurane does not mimic ischaemic preconditioning in decreasing hydroxyl radical production in the rabbit.

BACKGROUND: 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. METHODS: 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. RESULTS: 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, P<0.01). However, the increase observed in the isoflurane group was not different from control (71%). CONCLUSIONS: 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.

Ischaemic preconditioning but not isoflurane prevents post-ischaemic production of hydroxyl radicals in a canine model of ischaemia-reperfusion.

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 occlusion 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.

Myocardial infarction after vascular surgery: the role of prolonged stress-induced, ST depression-type ischemia.

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 ofischemia 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 (delta 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.

Perioperative myocardial ischemia in cataract surgery patients: general versus local anesthesia.

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) (P<0.05), and there were significantly more intraoperatively in the GA group (8 vs. 1) (P<0.01). 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.

Anaesthetic management of a patient undergoing reoperation for pathway obstruction after fontan operation.

Since 1968, the Fontan operation, or its various modifications, have provided a functional correction in an increasingly complex spectrum of congenital heart malformations.1.2 These procedures have gained wide acceptance because of very good intermediate and longterm results2. However, as survival increases, follow up of these patients has shown more prevalent reoperations for obstruction of the surgically created corrective pathway.3 perioperative management of these patients requires an understanding of the unique anatomic and physiologic changes occurring in this condition. In this report, we review our anaesthetic management of a patient who underwent reoperation for thrombotic occlusion of the conduit from a previous Fontan procedure.

Coronary spasm during outpatient fiberoptic laser bronchoscopy.

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.

Coronary Artery Bypass Grafting without Cardiopulmonary Bypass: Improvement in Cardiac Function Following Enflurane Anaesthesia during Coronary Occlusion.

Severe adverse effects, especially neurologic complications after cardiopulmonary bypass have lead to the development of techniques for performing coronary artery bypass graft surgery without cardiopulmonary bypass. Laboratory and clinical studies confirmed the positive role of enflurane anaesthesia in preventing myocardial dysfunction following an ischaemic interval. The aim of this study was to evaluate the haemodynamic response to enflurane anaesthesia during single graft coronary bypass surgery without cardiopulmonary bypass. Twenty one patients were divided randomly into two groups: control and enflurane groups. Haemodynamic parameters and those derived from a pulmonary artery catheter were recorded and analysed. In the enflurane group, the amount of fentanyl administered was considerably less than in the control group: 25.7 +/- 3.8 microg/kg vs 36.8 +/- 1.6; p=0.03. The mean arterial pressure during enflurane administration was lower than in control group, but the difference was not significant. Despite a dearease in left ventricular function during the performance of the anastomosis in the enflurane group, a significant recovery was noted after 20 minutes of reperfusion: cardiac index increased from 1.4 +/- 0.1 to 1.85 +/- 0.1 L/min/m2 and left ventricular stroke work index from 15.8 +/- 1.1 to 27.7 +/- 6.7 g.m.m2 . In the control group, the deterioration in cardiac function observed during the graft anastomosis did not recover till the end of the surgical procedure. We conclude that enflurane anaesthesia may be a positive addition to fentanyl-based anaesthesia by improving myocardial function following CABG without bypass surgery.

Halothane modifies oxygen free radical activity on the voltage-sensitive calcium channels in canine myocardial membranes.

BACKGROUND: The functional derangements in the myocyte cell membrane, the sarcolemma, during short myocardial ischaemia and reperfusion are attributed to excessive influx of Ca2+ ions via the voltage-sensitive calcium channels (VSCC) and to the free radical-related injury. However, it is unclear whether the primary changes in the VSCC should be attributed to the ischaemic effect or to free radical action on channel constituents. Under these circumstances of ischaemia and reperfusion, volatile anaesthetics have exhibited protective properties on the myocardium. The present study is aimed at characterizing the effect of artificially-generated oxygen free radicals on the VSCC in canine sarcolemma, independently of the effect of ischaemia, and the effect of halothane on the membranes during the surge of the free radicals. METHODS: Selective production of free radicals (O2-, CO2-) was made by gamma irradiation of isolated sarcolemma membranes with 137 Cesium (Cs), in the presence of 20 mM sodium formate. Control studies were performed without formate in the aqueous solution. In an additional group, liquid halothane (3 microl. 1.9 vol%) was added to the sarcolemma / formate preparation immediately prior to irradiation. The effects of free radicals on the VSCC was evaluated by redioligand binding studies of the calcium channel blocker [3H] isradipine to the sarcolemma. RESULTS: In six control studies, the rediolytic aqueous species produced by 137 Cs irradiation resulted in unchanged [3 H] isradipine binding. In the presence of formate [n=9], the free radicals have caused a 23% to 25% decrease, both, in density and dissociation constant (P=0.05) of [3 H]isradipine to the VSCC binding sites. When superoxide radicals were generated in the presence of 1.9% halothane and formate (n=6), a significant increase in maximal binding capacity (by 55% +/- 2; P<0.01) and in the dissociation constant (by 209% +/- 35, P<0.01) occurred. CONCLUSION: Oxidative free radicals which are generated by gamma irradiation exerted minimal changes on the normal function of the VSCC as reflected by the non-significant changes in [3 H] isradipine specific binding. Introduction of halothane into free radical generating system causes acute perturbations to the VSCC kinetics, and does not provide protection to the cardiac membranes.

ST segment changes following retinal surgery.

STUDY OBJECTIVE: To describe the perioperative cardiac morbidity in adult patients undergoing retinal surgery using continuous Holter monitoring. DESIGN: Prospective study. SETTING: University hospital. PATIENTS: 56 patients scheduled for elective retinal surgery with local anesthesia. INTERVENTIONS: 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. MEASUREMENTS AND MAIN RESULTS: 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 (p < 0.005), 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. CONCLUSION: 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.

Systolic pressure variation predicts the response to acute blood loss.

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.

Myocardial ischemia in sedated patients undergoing fiberoptic bronchoscopy.

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.

Cerebral protection using retrograde cerebral perfusion during hypothermic circulatory arrest.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Danaparoid for cardiopulmonary bypass in patients with previous heparin-induced thrombocytopenia.

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.

Halothane prevents postischemic production of hydroxyl radicals in the canine heart.

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.

Changes in cerebrospinal fluid pressure and lactate concentrations during thoracoabdominal aortic aneurysm surgery.

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.

Analysis of lysophophatidylcholine-induced endothelial dysfunction.

Endothelial dysfunction caused by the early atherosclerotic process or by endothelial exposure to atherogenic lipids, including lysophosphatidylcholine (lysoPC), is characterized by a selective impairment of responses mediated by the pertussis toxin-sensitive Gi-2 protein. Experiments were performed to analyze the mechanisms underlying this effect. Bradykinin (BK: Gi-2 protein-independent), serotonin (5-HT: Gi-2 protein-dependent), or direct activation of the G(i-2)-protein by mastoparan increased the release of endothelium-derived nitric oxide (EDNO) from porcine arterial endothelial cells (EC). LysoPC decreased the release of EDNO caused by 5-HT, but did not affect the response to BK or mastoparan. LysoPC did not increase production of superoxide radicals detected by lucigenin-enhanced chemiluminescence. Western blot analysis showed no difference in the level of immunoreactive Gi alpha-2 between control and lysoPC-treated cells. Activation of the Gi-2 protein by serotonergic or alpha 2-adrenoceptor stimulation decreased the pertussis toxin-catalyzed ADP-ribosylation of Gi alpha-2 protein in membranes from control but not lysoPC-treated cells. However, direct activation of the Gi-2 protein by mastoparan inhibited the ADP-ribosylation in membranes from control and lysoPC-treated cells. The toxin-catalyzed reaction was reduced in lysoPC-treated cells or lysoPC-treated membranes. LysoPC reduced the ability of endothelin to increase GTP gamma S binding to the Gi-2 protein but did not affect the activity of mastoparan. These results suggest that lysoPC inhibits a pertussis toxin-sensitive signaling pathway in EC by an effect consistent with receptor:Gi-2-protein uncoupling.

Normothermic continuous blood cardioplegia improves electrophysiologic recovery after open heart surgery.

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.

Luke warm blood cardioplegia for CAB surgery in patients with severely impaired LV function. Improved results.

Ward blood cardioplegia (WBC) has recently been reported to improve myocardial protection in adult open heart surgery, especially in high risk cases. However, WBC has been reported to have some disadvantages including narrow safety margins concerning brain and kidney perfusion. We therefore modified our technique to utilize luke-warm blood cardioplegia (LWBC). We carried out 470 open heart procedures using luke-warm cardioplegia (anterograde + retrograde perfusion) from 1/2/1991 - 30/9/1992; 94 had LVEF < 30% and form the basis of this study. Other major risk factors in this group included: > 70 yrs - 26 patients, L main > 50% - 14 patients, emergencies - 11 patients, redo's - 3 patients. Eightyone patients underwent CAB only; 3 had additional MVR, 3 additional closure acute VSD of whom one underwent additional LV aneurysmectomy, one additional AVR; 4 patients underwent AVR only, and 2 MVR. Average number of grafts/patient for the 81 isolated CAB's was 4.5. IABP was necessary postbypass in 4 patients (9 emergencies were on IABP support at time of operation). Thirty day mortality was 3 patients (3.2%). Late mortality was 5 cases. These results are superior to those achieved using cold protection and warm blood cardioplegia. LWBC is a safe method for myocardial protection in patients undergoing CAB, particularly when LV function is severely compromised.