Amir Elami

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 ([center dot] 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 [center dot] 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.

Tetralogy of Fallot, absent pulmonary valve, partial anomalous pulmonary venous return and coarctation of the aorta

We describe a unique combination of tetralogy of Fallot, absent pulmonary valve, aortic coarctation with partial anomalous pulmonary venous connection and a retroaortic innominate vein. Surgical repair was successfully accomplished in two stages: coarctation repair preceded correction of the intracardiac anomalies.

Suicide bombing injuries: the Jerusalem experience of exceptional tissue damage posing a new challenge for the reconstructive surgeon

Background: Suicide bomb injuries vary in form and magnitude. From the onset of the second Palestinian “intifada” in October of 2000 until January of 2004, 577 victims of suicide bombings were admitted to the Hadassah-Hebrew University Medical Center. A single bomber carrying a handbag or belt containing multiple metal objects and explosives carried out most of the attacks. As a result, many of the victims suffered massive tissue destruction in addition to conventional blast injuries. Methods: This article describes the management of this trauma-related “syndrome” of combined primary and high-magnitude secondary blast injury. Results: The management of the extensive soft-tissue damage is described and two representative cases presented. Conclusion: Suicide bombing–related injuries in their present form are a true challenge for the reconstructive surgeon.

Positive end-expiratory pressure increases pulmonary venous vascular resistance in patients after coronary artery surgery

OBJECTIVE To investigate the effect of positive and-expiratory pressure (PEEP) on the longitudinal distribution of pulmonary vascular resistance in patients immediately after coronary artery bypass grafting. DESIGN Prospective, intervention study. SETTING Postcardiac surgery intensive care unit in a teaching institution. PATIENTS Twenty patients after elective coronary artery bypass grafting. INTERVENTION The effect of PEEP on pulmonary circulation, at four different levels (0, 5, 10, and 15 cm H2O), was analyzed in 20 patients. MEASUREMENTS AND MAIN RESULTS Mean pulmonary arterial pressure, left atrial pressure, pulmonary artery occlusion pressure, and pulmonary capillary pressure were measured at each PEEP level. A model consisting of two resistances in series was used to analyze the effect of PEEP on the pulmonary circulation. The pulmonary vascular resistance for each area (arterial and venous) of the circulation was calculated. Pulmonary vascular resistance increased from 216 +/- 70 dyne.sec/cm5 at a PEEP of 0 cm H2O to 308 +/- 125 dyne.sec/cm5 at a PEEP of 15 cm H2O (p < .001). This increase, however, resulted solely from an increase in the resistance of the venous part of the pulmonary circulation from 66 +/- 29 to 134 +/- 69 dyne.sec/cm5 (p < .001), without any change in pulmonary arterial resistance. CONCLUSIONS PEEP increases pulmonary vascular resistance solely by increasing pulmonary venous resistance. When applying PEEP, changes in pulmonary vascular resistance may impede the resorption of pulmonary edema fluid.

Successful restoration of function of frozen and thawed isolated rat hearts

OBJECTIVE Long-term organ preservation for transplantation may allow optimal donor-recipient matching with potential reduction in the incidence and severity of rejection. Complete cessation of metabolism may be obtained by freezing. Previous attempts to freeze intact mammalian hearts were limited to -3.6 degrees C, restricting tissue ice content to 34%. We hypothesized that our method will allow recovery of function of the intact rat heart after freezing to -8 degrees C, a temperature at which most of the tissue water is frozen. METHODS Isolated rat hearts were attached to a Langendorff apparatus. After normothermic perfusion, cold cardioplegia was induced followed by perfusion with a cryoprotecting agent. Hearts were than frozen to -8 degrees C (45 +/- 8 minutes), thawed, and reperfused (60 minutes). RESULTS All frozen and thawed hearts regained normal electric activity. At -8 degrees C, ice content was 64.36% +/- 13%. The use of 10% ethylene glycol for cryoprotection (n = 13) resulted in recovery (mean +/- standard deviation) of 49.7% +/- 21.8% of +dP/dt, 48.0% +/- 23.5% of -dP/dt, 65.2% +/- 30.8% of coronary flow, and 50.4% +/- 23.9% of left ventricular developed pressure. Hearts in this group (n = 4) maintained 81.3% +/- 10% viability compared with 69.3% +/- 14% (not significant) in control hearts kept at 0 degrees C for the same duration. Energy stores, represented by adenosine triphosphate and phosphocreatine, were depleted to 12.2 +/- 6.1 micromol/g dry weight and 22.5 +/- 6.4 micromol/g dry weight, respectively, compared with 19.0 +/- 2.5 micromol/g dry weight and 36.6 +/- 3.0 micromol/g dry weight, respectively (P < .05) in the control hearts. The integrity of muscle fibers and intracellular organelles after thawing and reperfusion was demonstrated by electron microscopy. CONCLUSION We demonstrate for the first time the feasibility of functional recovery after freezing and thawing of the isolated rat heart while maintaining structural integrity and viability.

Impaired oxygenation and increased hemolysis after cardiopulmonary bypass in patients with glucose-6-phosphate dehydrogenase deficiency

BACKGROUND The purpose of this study was to determine whether the damaging effects of cardiopulmonary bypass, ischemia, and reperfusion would be more pronounced in patients with glucose-6-phosphate dehydrogenase deficiency undergoing cardiac surgery. METHODS Forty-two patients with glucose-6-phosphate dehydrogenase deficiency underwent open heart procedures using cardiopulmonary bypass. This group was matched with a control group of identical size for comparison of operative course and postoperative outcome. The perioperative variables were compared between the two groups using univariate and multivariate analysis. RESULTS The duration of ventilation after the operation was significantly longer in the glucose-6-phosphate dehydrogenase-deficient group (13.7 +/- 7.6 hours versus 7.7 +/- 2.8 hours; p < 0.0001). Minimal value of arterial oxygen tension was lower in patients with glucose-6-phosphate dehydrogenase deficiency (66 +/- 12 mm Hg versus 85 +/- 14 mm Hg; p < 0.0001), and more cases of hypoxia (arterial oxygen tension < 60 mm Hg) were found in this group (11 versus 1; p = 0.001). Compared with the control group, patients with glucose-6-phosphate dehydrogenase deficiency had significantly elevated hemolytic indices expressed by bilirubin levels (26 +/- 10 mmol/L versus 17 +/- 6.7 mmol/L; p < 0.0001) and lactic dehydrogenase levels (970 +/- 496 U/L versus 505 +/- 195 U/L; p < 0.0001). They also required significantly more blood transfusion perioperatively (1.9 +/- 1.4 packed cell units/patient versus 0.8 +/- 1.0 packed cell units/patient; p = 0.0001). CONCLUSIONS Patients with glucose-6-phosphate dehydrogenase deficiency who are undergoing cardiac surgery may have a more complicated course with a longer ventilation time, more hypoxia, increased hemolysis, and a need for more blood transfusion. Because this difference may be caused by subnormal free radical deactivation, strategies that minimize bypass in general and free radicals specifically may be beneficial.

Myocardial Metabolism Altered by Ischemic Preconditioning and Enflurane in Off-Pump Coronary Artery Surgery

OBJECTIVE 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. DESIGN A prospective, randomized, controlled, and partly blinded study. SETTING A tertiary care university hospital. PARTICIPANTS Twenty-five patients undergoing elective single-graft OPCAB surgery. INTERVENTIONS 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. MEASUREMENTS AND MAIN RESULTS Although the hemodynamic changes were small, myocardial lactate production in the control group increased by 120%, whereas in the enflurane group it decreased significantly (p < 0.01) compared with the control and IPC groups. Oxygen utilization in the control group was 44% higher (p < 0.03), and there was also a larger release of the hydroxyl radical-dependent adduct 2,3-dihydroxybenzoic acid (225% increase, p < 0.05) 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. CONCLUSIONS 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.

Future strategies for the treatment of diastolic heart failure

It is estimated that 30% to 50% of heart failure patients have preserved systolic left ventricular (LV) function, often referred to as diastolic heart failure (DHF). Mortality is high in this patient population, and morbidity and rate of hospitalization are similar to those of patients with systolic heart failure. The management of patients with diastolic heart failure is essentially empirical, limited, and disappointing. New drugs, devices, and gene therapy based treatment options are currently under investigation. In this review, future strategies for the treatment of diastolic heart failure are discussed.

Cerebral protection using retrograde cerebral perfusion during hypothermic circulatory arrest

BackgroundRetrograde cerebral perfusion through the superior vena cava (SVC) has been proposed to protect the brain from ischaemic injury during profound hypothemnic 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.MethodsIn three patients undergoing repair of the ascending aorta utilizing PHCA, the upper body was retrogradely perfused with cold (16°C) blood through the SVC by the cardiopulmonary bypass pump. Electroencephalographic activity was monitored using a computenzed 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.ResultsDuring PHCA penods 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 μg) and nitroglycerin (2 μg · 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.ConclusionInjection of anaesthetic agents into the retrograde SVC perfusate during PHCA, can suppress reoccumng electroencephalographic activity and retrograde injection of vasodilators can facilitate an increase in perfusion. It is suggested that both may augment brain protection.RésuméObjectifLa perfusion cérébrale rétrograde par la veine cave supérieure (VCS) pourrait protéger le cerveau de l’ischémie pendant l’arrêt circulatoire en hypothermie profonde (ACHP) mais cette hypothèse n’est pas prouvée. En outre, on n’a jamais rapporté non plus que les agents anesthésiques ou vasodilatateurs ajoutés au liquide de perfusion de la VCS amplifiaient la protection cérébrale.MéthodesAu cours d’une réparation de l’aorte ascendante sous ACHP, on a perfusé la partie supérieure du corps de trois patients par voie rétrograde avec du sang froid (16C) par la VCS à l’aide d’une pompe de circulation extracorponelle. Un moniteur informatisé (Cenebro Trac 2500, SRD) a servi a monrtorer l’activité électroencéphalographique. La pression de perfusion était mesurée par un orifice situé sur la canule. L’activité électroencéphalographique était interrompue par l’injection dans le liquide de perfusion de la VCS d’étomidate et de thiopental. Le nitroprussiate et la nitroglycénne étaient ajoutés au perfusat afin d’augmenter le flux rétrograde et maintenir constante la pression de perfusion.RésultatsL’admmistration rétrograde de petits bolus d’étomidate (total 50 mg) ou de thiopental (total 500 mg) a aboli la reprise de l’activité électroencéphalographique pendant 61 min d’ACPH ou moins. Le nitroprussiate (100 μg) et la nitroglycérine (2 μg · kg−1 · min−1) ont accru le flux rétrograde de 220 à 550 et à 660 ml · min−1 respectivement, tout en maintenant la pression de perfusion constante (25–26 mmHg). La récupération anesthésique et chirurgicale s’est deroulee sans problèmes ni séquelles neurologiques.ConclusionLinjection d’agents anesthésiques dans le liquide de perfusion rétrograde de la VCS pendant l’ACPH peut suppnmer la repnse de l’activité électroencéphalographique. L’injection rétrograde de vasodilatateurs peut favoriser l’augmentation de la perfusion. Ces deux interventions pourraient accroître la protection cérébrale.

Energy transfer from systole to diastole: A novel device-based approach for the treatment of diastolic heart failure

We hypothesized that attachment of elastic coil to the left ventricular (LV) wall, capable of exerting outward forces may allow the transfer of energy from systole to diastole and improve diastolic function. Methods and results: An extra-ventricular-device, composed of a series of elastic elements interposed between spiral screws attached to the epimyocardium of the LV free-wall was developed. The hemodynamic and mechanical effects of the device were tested using a computerized model, an in vitro model utilizing a computerized-controlled fluid pump, eight healthy sheep and 10 mini-pigs induced with diastolic dysfunction by renal wrapping. The computerized and in vitro models predicted a reduction of the LV diastolic pressure curve and partial normalization of the pressure-volume loop. The sheep study demonstrated preservation of animals wellbeing including maintaining cardiac mechanical function with stable energy transfer from systole to diastole throughout the 6 months follow-up. The mini-pigs study showed an increase in the early diastolic to systolic strain-rate ratio in the mid-endocardial level (23 ± 10%, P = 0.008) and an increase in early apical reverse rotation rate of 50% (P = 0.016 compared to control). Conclusions: This study presents a novel concept of using a mechanical device to transfer energy from systole to diastole, potentially enhancing diastolic function.