Changes in regional cerebral blood flow under hypothermic selective cerebral perfusion.

OBJECTIVE: Currently the most frequently used perfusion technique during aortic arch surgery to prevent cerebral damage is hypothermic selective cerebral perfusion (SCP). Changes in cerebral blood flow (CBF) are known to occur during these procedures. We investigated regional changes of CBF under conditions of SCP in a porcine model. METHODS: In this blinded study, twenty-three juvenile pigs (20 - 22 kg) were randomized after cooling to 20 degrees C on CPB. Group I (n = 12) underwent SCP for 90 minutes, while group II (n = 11) underwent total body perfusion. Fluorescent microspheres were injected at seven time-points to calculate total and regional CBF. Hemodynamics, intracranial pressure (ICP), cerebrovascular resistance (CVR) and oxygen consumption were assessed. Tissue samples from the neocortex, cerebellum, hippocampus and brain stem were taken for a microsphere count. RESULTS: CBF decreased significantly (p = 0.0001) during cooling, but remained at significantly higher levels with SCP than with CPB throughout perfusion (p < 0.0001) and recovery (p < 0.0001). These findings were similar among all regions of the brain, certainly at different levels. Neocortex CBF decreased 50%, whereas brain stem and hippocampus CBF decreased by only 25 % during total body perfusion. All four regions showed 10 - 20% less CBF in the post-CPB period. CBF during SCP did not fall by more than 20% in any analysed region. The hippocampus turned out to have the lowest CBF, while the neocortex showed the highest CBF. CONCLUSION: SCP improves CBF in all regions of the brain. Our study characterizes the brain specific hierarchy of blood flow during SCP and total body perfusion. These dynamics are highly relevant for clinical strategies of perfusion.

Retrograde cerebral perfusion provides negligible flow through brain capillaries in the pig.

OBJECTIVES: Although retrograde cerebral perfusion is being used clinically during aortic arch surgery, whether retrograde flow perfuses the brain effectively is still uncertain. METHODS: Fourteen pigs were cooled to 20 degrees C with cardiopulmonary bypass and perfused retrogradely via the superior vena cava for 30 minutes: 7 underwent standard retrograde cerebral perfusion and 7 underwent retrograde perfusion with occlusion of the inferior vena cava. Antegrade and retrograde cerebral blood flow were calculated by quantitating fluorescent microspheres trapped in brain tissue after the animals were put to death; microspheres returning to the aortic arch, the inferior vena cava, and the descending aorta were also analyzed during retrograde cerebral perfusion. RESULTS: Antegrade cerebral blood flow was 16 +/- 7.7 mL. min(-1). 100 g(-1) before retrograde cerebral perfusion and 22 +/- 6.3 mL. min(-1). 100 g(-1) before perfusion with caval occlusion (P =.14). During retrograde perfusion, calculations based on the number of microspheres trapped in the brain showed negligible flows (0.02 +/- 0.02 mL. min(-1). 100 g(-1) with retrograde cerebral perfusion and 0.04 +/- 0.02 mL. min(-1). 100 g(-1) with perfusion with caval occlusion; P =.09): only 0.01% and 0.02% of superior vena caval inflow, respectively. Less than 13% of retrograde superior vena caval inflow blood returned to the aortic arch with either technique. During retrograde cerebral perfusion, more than 90% of superior vena caval input was shunted to the inferior vena cava and was then recirculated, as indicated by rapid development of an equilibrium in microspheres between the superior and inferior venae cavae. With retrograde perfusion and inferior vena caval occlusion, less than 12% of inflow returned to the descending aorta and only 0.01% of microspheres. CONCLUSIONS: The paucity of microspheres trapped within the brain indicates that retrograde cerebral perfusion, either alone or combined with inferior vena caval occlusion, does not provide sufficient cerebral capillary perfusion to confer any metabolic benefit. The slightly improved outcome previously reported with retrograde cerebral perfusion during prolonged circulatory arrest in this model may be a consequence of enhanced cooling resulting from perfusion of nonbrain capillaries and from venoarterial and venovenous shunting.

Cyclosporine A as a potential neuroprotective agent: a study of prolonged hypothermic circulatory arrest in a chronic porcine model.

OBJECTIVE: To assess whether Cyclosporine A (CsA) or cycloheximide (CHX) can reduce ischemia-induced neurological damage by blocking apoptotic pathways, we assessed their effects on cerebral recovery in a chronic animal model of hypothermic circulatory arrest (HCA). METHODS: Twenty-eight pigs (28-33 kg) underwent 90 min of HCA at 20 degrees C. In this blinded study, animals were randomized to placebo (n=12), 5 mg/kg CsA (n=8), given intravenously before and subcutaneously for 7 days after HCA, or a single dose of 1 mg/kg CHX (n=8), given after weaning from cardiopulmonary bypass. Hemodynamics, intracranial pressure (ICP) and neurophysiological data (EEG, SSEP) were assessed for 3 h after HCA; early behavioral recovery was scored, and neurological/behavioral evaluation (9=normal) was carried out daily until elective sacrifice on postoperative day (POD) 7. Brains were selectively perfused and evaluated histopathologically for apoptosis. RESULTS: Basic hemodynamic data revealed no differences between CsA or CHX and control groups. ICP was significantly lower throughout rewarming (P=0.009) and reperfusion (P=0.05) in the CsA group. EEG recovery 3 h after HCA was observed in four of eight CsA animals but in only 1 of 12 controls (P=0.11) and one of eight CHX animals; cortical SSEP recovery also seemed faster in CsA animals, but failed to reach significance. Some early recovery scores were significantly better in the CsA group, and daily behavioral scores were consistently and significantly higher in the CsA-treated animals from POD1 through POD4. CONCLUSIONS: The data indicate that treatment with Cyclosporine A but not cycloheximide has a positive effect on cerebral recovery following HCA. Whether CsA results in inhibition of neuronal apoptosis, and/or inhibits release of cytokines and thereby reduces postischemic cerebral edema remains to be elucidated. The neuroprotective effect of CsA, if confirmed in further studies, would make its clinical application conceivable.

Cerebral effects of cold reperfusion after hypothermic circulatory arrest.

OBJECTIVES: This study was undertaken to explore whether an interval of cold reperfusion can improve cerebral outcome after prolonged hypothermic circulatory arrest. METHODS: Sixteen pigs (27-30 kg) underwent 90 minutes of circulatory arrest at a brain temperature of 20 degrees C. Eight animals were rewarmed immediately after hypothermic circulatory arrest (controls), and 8 were reperfused for 20 minutes at 20 degrees C and then rewarmed (cold reperfusion). Electrophysiologic recordings, fluorescent microsphere determinations of cerebral blood flow, calculations of cerebral oxygen consumption, and direct measurements of intracranial pressure (millimeters of mercury) were obtained at baseline (37 degrees C), before hypothermic circulatory arrest, after discontinuing circulatory arrest at 37 degrees C deep brain temperature, and at 2, 4, and 6 hours thereafter. Histopathologic features and percent brain water were determined after the animals were sacrificed. RESULTS: Cerebral blood flow and oxygen consumption decreased during cooling: cerebral oxygen consumption returned to baseline levels after 4 hours, but cerebral blood flow remained depressed until 6 hours in both groups. Cold reperfusion failed to improve electrophysiologic recovery or to reduce brain weight, but median intracranial pressure increased significantly less after cold reperfusion than in controls (P =.02). Although no significant difference in the incidence of histopathologic abnormalities between groups was found, all 3 animals with an intracranial pressure of more than 15 mm Hg after immediate rewarming had histopathologic lesions, and high intracranial pressure was more prevalent among all animals with subsequent histopathologic lesions (P =.03). CONCLUSIONS: Cold reperfusion significantly inhibited the rise in intracranial pressure seen in control pigs after 90 minutes of circulatory arrest at 20 degrees C, suggesting that cold reperfusion may decrease cerebral edema and thereby improve outcome after prolonged hypothermic circulatory arrest.

Milrinone is superior to epinephrine as treatment of myocardial depression due to ropivacaine in pigs.

PURPOSE: To determine whether milrinone is more effective than epinephrine in the resuscitation of ropivacaine induced cardiotoxicity in pigs. METHODS: Arterial, pulmonary, and LVdP/dt catheters were placed in 12 anesthetized, intubated and mechanically ventilated pigs. They received ropivacaine iv to cardiovascular toxicity: 50% decrease in LVdP/dt, cardiac output and mean arterial pressure (MAP). Group I (n=6) was treated with 100 microg x kg(-1) milrinone iv, and Group II (n=6) received 0.5 mg epinephrine iv. Resuscitation was successful if cardiac output returned to baseline, and MAP reached 80% of baseline. RESULTS: After ropivacaine, MAP decreased from 88 +/- 7 to 49 +/- 8 mmHg (P < 0.05), CO decreased from 2.8 +/- 0.4 to 1.2 +/- 0.2 L x min(-1) (P < .05), HR decreased from 103 +/- 8 to 74 +/- 7 beats x min (P < 0.05) and LVdp/dt decreased from 1,950 +/- 130 to 755 +/- 125 mmHg (P < 0.05). The LV EDP increased from 5 +/- 1 to 8 +/- 1 mmHg (P < 0.05) and SVR from 2,317 to 3,000 +/- 120 dynes x sec(-1) x cm(-5). Electrocardiogram changes included increases in the QTU interval and QRS duration. In all animals, milrinone restored MAP, CO, SV, HR, and dP/dt to baseline and no animal developed arrhythmias. In contrast, epinephrine produced severe hypertension and tachycardia. There was no improvement in CO or SV, and SVR increased. Epinephrine caused A-V dissociation and ventricular arrhythmias in three animals. CONCLUSION: Milrinone, was more successful than epinephrine in resuscitating anesthetized pigs from ropivacaine-induced cardiovascular toxicity.

Retrograde cerebral perfusion enhances cerebral protection during prolonged hypothermic circulatory arrest: a study in a chronic porcine model.

BACKGROUND: This study was undertaken to confirm earlier findings that retrograde cerebral perfusion (RCP) can improve cerebral outcome after prolonged hypothermic circulatory arrest (HCA), and to determine whether RCP with inferior vena caval occlusion, which is more effective in removing particulate emboli, is superior to conventional RCP in enhancing cerebral protection. METHODS: Sixty-two pigs (27 to 30 kg) were randomly assigned to undergo one of the following for 90 minutes at 20 degrees C: antegrade cerebral perfusion (ACP); conventional RCP (RCP); RCP with occlusion of the inferior vena cava (RCP-O), or HCA with the head packed in ice. RCP flow was regulated to a sagittal sinus pressure of 20 mm Hg. Hemodynamic, electrophysiologic, and metabolic monitoring were carried out until 4 hours after rewarming, daily behavioral and neurologic assessments until elective sacrifice on day 7, and histologic analysis of the brain after death. RESULTS: Complete behavioral recovery was seen in all surviving animals by day 5 after ACP or RCP, but in only 83% after RCP-O and 50% after HCA (p = 0.001). A histopathologic score of 2 or more, indicating more than mild injury, was not found in any animal after ACP, in 27% after RCP, in 47% after HCA, and in 68% after RCP-O (p = 0.002). The median oxygen consumption was 6.66 mL/min after ACP, 1.37 mL/min with RCP, and 1.02 mL/min with RCP-O (p < 0.0001). The median amount of fluid sequestered was 2,450 mL after RCP-O, 760 mL after RCP, and -200 mL after ACP (p < 0.0001). CONCLUSIONS: Conventional RCP without inferior vena caval occlusion results in a significantly better outcome than RCP-O after prolonged HCA, despite more efficient cerebral perfusion during RCP-O, and also provides cerebral protection superior to prolonged HCA alone, but care must be taken during its implementation to minimize cerebral edema and other possible causes of retroperfusion-related cerebral injury.

Cardiovascular consequences of the concomitant administration of nifedipine and magnesium sulfate in pigs.

There is concern regarding the interaction of magnesium sulfate and nifedipine used concomitantly in obstetrical patients, because both are calcium channel antagonists and may induce myocardial depression as well as peripheral vasodilatation. The objective of this study was to determine the hemodynamic consequences of concomitant administration of nifedipine and magnesium sulfate in anesthetized pigs. Twelve pigs were anesthetized with sodium pentobarbital, intubated mechanically ventilated. Following placement of invasive monitors, baseline hemodynamic measurements were made. Animals were randomized to one of two groups. Group I received nifedipine first, and then magnesium sulfate. Group II received magnesium sulfate first, and then nifedipine. Hemodynamic measurements were recorded. Hypotension was treated with calcium chloride, ephedrine and phenylephrine. Nifedipine alone (Group I) decreased peripheral vascular resistance and mean arterial pressure (MAP) (P<0.05). Magnesium sulfate alone in group II decreased the first derivative of left ventricular pressure (LVdP/dt) and increased left ventricular end-diastolic pressure (LVEDP) (P<0.05). Magnesium sulfate also decreased peripheral vascular resistance and MAP The concomitant administration of nifedipine and magnesium sulfate in both groups I and 11 led to a further decrease in myocardial contractility, as evidenced by a decrease in LVdP/dt and increase in LVEDP (P<0.05). Treatment with calcium chloride or ephedrine was only partially successful in improving myocardial contractility. Phenylephrine increased peripheral vascular resistance and MAP, but did not improve myocardial function. In conclusion, the depressive effects of nifedipine and magnesium sulfate on the cardiovascular system are potentiated when administered concomitantly.

Role of zatebradine and propranolol in attenuation of tachycardia produced by dobutamine in pigs.

BACKGROUND: Zatebradine is a new specific bradycardiac agent that selectively slows the depolarization in the pacemaker cells of the sinoatrial node. The purpose of our investigation was to determine whether the tachycardia induced by dobutamine can be attenuated by the administration of zatebradine. The results were compared with those produced by propranolol, which is used in the treatment of sinus tachycardia. METHODS: Twelve pigs were anesthetized with sodium pentobarbital, intubated, and ventilated. After baseline hemodynamic measurements were obtained, dobutamine was administered until the heart rate reached 25% above baseline. Animals were randomized to one of two groups. Group I received zatebradine, 0.5 mg/kg i.v., and Group II received propranolol, 0.5 mg/kg i.v. RESULTS: Dobutamine 10 micrograms.kg-1.min-1 increased the heart rate (FIR) by 25%, and increased mean arterial blood pressure (MAP) left ventricular (LV) dp/dt, and cardiac output (CO) (P < 0.05). Zatebradine decreased the HR to baseline (P < 0.05) without affecting left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), LV dP/dt, or CO. Stroke volume (SV) increased significantly (P < 0.05). Propranolol also reduced HR to baseline, but decreased LV dP/dt, LVSP, CO, and SV (P < 0.05). CONCLUSION: Zatebradine effectively attenuates the tachycardia caused by dobutamine in anesthetized pigs, without reducing cardiac performance.

The effect of retrograde cerebral perfusion after particulate embolization to the brain.

Neurologic injury as a consequence of cerebral embolism of either air or atherosclerotic debris during cardiac or aortic surgery is still a major cause of postoperative morbidity and mortality. While exploring various means of improving cerebral protection during complex cardiothoracic procedures, we have developed a chronic porcine model to study retrograde cerebral perfusion. We have previously demonstrated that retrograde perfusion results in a small amount of nutritive flow and provides cerebral protection that appears to be superior to simple prolonged hypothermic circulatory arrest. The current study was designed to evaluate the efficacy of retrograde cerebral perfusion in mitigating the effects of particulate cerebral embolism occurring during cardiac surgery. Four groups of pigs (19 to 28 kg) underwent cardiopulmonary bypass with deep hypothermia at an esophageal temperature of 20 degrees C: an antegrade control group (AC, n = 5), an antegrade embolism group (AE, n = 10), a retrograde control group (RC, n = 5), and a retrograde embolism group (RE, n = 10). In addition, because of extreme heterogeneity in outcome in the initial RE group, an additional group of 10 animals underwent embolism and retrograde perfusion at a later time. Embolization was accomplished by injection of 200 mg of polystyrene microspheres (250 to 750 micrograms in diameter) via the aortic cannula into an isolated aortic arch preparation in the AE and RE groups; the control groups received injections of 10 ml of saline solution. After infusion of the microspheres or saline solution, conventional perfusion, with the aortic arch pressure maintained at 50 mm Hg, was continued for a total of 30 minutes in the antegrade groups; in the retrograde groups, retrograde flow was initiated via a cannula positioned in the superior vena cava, and was continued for 25 minutes. Superior vena caval flow was regulated to maintain a sagittal sinus pressure of approximately 30 mm Hg in the retrograde groups, and blood returning to the isolated aortic arch was collected and measured. All animals were allowed to recover and were evaluated daily according to a quantitative behavioral score in which 9 indicates apparently complete normalcy, with lower numbers indicating various degrees of cerebral injury. At the time of planned death on day 6, half of the brain was used for recovery of embolized microspheres after digestion with 10N sodium hydroxide. The other half was submitted for histologic study. Neurologic recovery in both the antegrade and retrograde control groups appeared to be complete, although mild evidence of histologic damage was present in some animals in the retrograde control group.(ABSTRACT TRUNCATED AT 400 WORDS)

Metabolic correlates of neurologic and behavioral injury after prolonged hypothermic circulatory arrest.

Thirty-two inbred weanling puppies were divided into four groups to study the effect on cerebral blood flow and metabolism of different hypothermic strategies for cerebral protection similar to those used during cardiac operations in infancy. All animals were cooled to 18 degrees C. The animals in the hypothermic control group were immediately rewarmed. One group underwent 30 minutes of hypothermic circulatory arrest at 18 degrees C; another group had 90 minutes of hypothermic circulatory arrest at 18 degrees C, and the final group had low-flow cardiopulmonary bypass (25 ml/kg per minute) at 18 degrees C for 90 minutes. All animals had preoperative and postoperative neurologic and behavioral evaluation and extensive intraoperative monitoring of cerebral blood flow, cerebral vascular resistance, and oxygen and glucose uptake and metabolism: quantitative electroencephalography was also monitored before, during and after operation, but those results are reported separately. Two animals in the 90-minute arrest group died, and all the survivors showed evidence of clinical, neurologic, and behavioral impairment on postoperative day 1, with residual abnormalities in all but one animal on day 6. In contrast, the survivors in all the other groups showed no significant clinical or behavioral sequelae. Cerebral metabolism was reduced only to 32% to 40% of baseline values at 18 degrees C in all groups, although systemic metabolism was only 16% of normal. Cerebral metabolism returned promptly to baseline in all groups during rewarming and remained at baseline levels throughout the 8 hours of follow-up. Cerebral blood flow showed marked hyperemia in the hypothermic arrest groups during rewarming but then significant reductions below baseline values in all groups except the controls at 2 and 4 hours after the operation, lasting as late as 8 hours after the operation in the 90-minute arrest group. Cerebral vascular resistance showed increases in all groups at 2 and 4 hours after the operation, which persisted in the 90-minute arrest group at 8 hours. Cerebral metabolism was maintained at baseline levels despite postoperative decreases in cerebral blood flow and increases in cerebral vascular resistance by increases in oxygen and glucose extraction. The result was very low sagittal sinus oxygen saturations in all groups, most marked in the 90-minute arrest groups, which had a saturation of only 24% 8 hours after the operation. Our data show a severe, prolonged disturbance in cerebral blood flow and cerebral vascular resistance after 90 minutes of hypothermic circulatory arrest at 18 degrees C, which correlates with clinical evidence of cerebral injury.(ABSTRACT TRUNCATED AT 400 WORDS)

Arrhythmogenic potential of dopexamine hydrochloride during halothane anaesthesia in dogs.

Dopexamine hydrochloride (Dopacard) is the novel synthetic catecholamine designed for use in the acute management of a low cardiac output status. In addition to dopaminergic receptor stimulation, dopexamine hydrochloride is a potent beta 2 adrenoceptor agonist with negligible direct beta 1 and no alpha adrenergic effect. The objective of this study was to compare the arrhythmogenic effects of dopexamine hydrochloride and dopamine in dogs anaesthetized with halothane (1.2 MAC). The starting dose for dopexamine hydrochloride was 3.5 micrograms.kg-1.min-1 and for dopamine was 5 micrograms.kg-1.min-1. Concentrations of the drugs were increased until four or more premature ventricular contractions within 15 seconds were produced. All dogs developed ventricular tachycardia when dopamine was administered in concentrations ranging between 18-20 micrograms.kg-1.min-1. Unlike dopamine, dopexamine hydrochloride even at concentrations as high as 50 micrograms.kg-1.min-1 did not induce any atrial or ventricular ectopic beats. Lack of beta 1 and alpha adrenergic agonist effects is a likely explanation for low arrhythmogenicity of dopexamine hydrochloride. Both drugs increase cardiac output; dopexamine hydrochloride primarily by a dose-related increase in heart rate and increased afterload. At the maximal concentration dopexamine hydrochloride increased heart rate from 114 to 150 beat.min-1, mean arterial pressure decreased from 81 mmHg to 45 mmHg and SVR decreased from 2418 to 962 dyne.sec-1cm-5. Myocardial contractility increased only moderately, as evaluated by dP/dt, which increased from 1290 to 1696 mmHg.sec-1. Dopamine had a more marked inotropic effect: the dP/dt increased, at the maximal concentration, from 1480 to 2570 mmHg.sec-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral effects of low-flow cardiopulmonary bypass and hypothermic circulatory arrest.

Although both hypothermic circulatory arrest (HCA) and low-flow cardiopulmonary bypass (CPB) are accepted techniques for the operative management of complex cardiovascular pathology, the potential for neurologic sequelae is still a concern. To assess the relative safety of these techniques, we compared cerebral hemodynamics and clinical outcome in two groups of puppies. Sixteen puppies underwent 45 minutes of either HCA or low-flow CPB (25 mL.kg-1.min-1) after cooling to 13 degrees C. Methodology included radioactive microsphere determination of cerebral blood flow; calculation of cerebral oxygen extraction (arteriovenous oxygen content difference) and consumption; measurement of glucose consumption, and determination of cerebrovascular resistance. Measurements were obtained at baseline (37 degrees C), 13 degrees C, and 30 degrees C and at 2, 4, and 8 hours after HCA or low-flow CPB. No neurologic deficits were observed in any of the survivors (15/16). In both groups, cerebral metabolic rate of oxygen was maintained at baseline or greater levels postoperatively. Cerebrovascular resistance rose slightly in the low-flow CPB group postoperatively in contrast to a marked elevation in the HCA group. During the period of high cerebrovascular resistance after HCA, cerebral metabolic rate of oxygen was maintained by increased oxygen extraction. After low-flow CPB, oxygen extraction was not significantly different from baseline, presumably because of less severe changes in cerebrovascular resistance. Glucose metabolism followed the same trends as oxygen metabolism in both groups. These data suggest that after HCA there is a vulnerable interval, lasting as late as 8 hours postoperatively, in which cerebrovascular resistance remains high and cerebral metabolism is maintained primarily by high oxygen and glucose extraction. Any additional stress during this interval (a decrease in arterial oxygen content or perfusion pressure) could result in cerebral injury.

Cerebral blood flow and metabolism in hypothermic circulatory arrest.

Although hypothermic circulatory arrest has been accepted for use in cardiovascular operations, the potential for cerebral injury exists. The mechanism of the cerebral injury remains unclear. To address these questions we studied cerebral blood flow and metabolism. Sixteen puppies were randomly assigned to undergo either 45 or 90 minutes of hypothermic circulatory arrest after perfusion/surface cooling to 13 degrees C. Cerebral blood flow, cerebral oxygen and glucose metabolism, and cerebral vascular resistance measurements were obtained at 37 degrees C, 13 degrees C, 10 minutes after reperfusion, 30 degrees C and 2 and 4 hours after hypothermic circulatory arrest. No neurologic or behavioral changes were observed in any of the long-term survivors (11/16). Metabolic and cerebral blood flow data did not differ between groups. Cerebral blood flow was significantly lower in the late postarrest measurements, whereas oxygen and glucose consumption had returned to baseline values. In the presence of low cerebral blood flow and high cerebral vascular resistance it is notable that control levels of oxygen consumption were attained by abnormally high oxygen extraction. These data strongly suggest a vulnerable interval after hypothermic circulatory arrest in which cerebral metabolism is limited by cerebral blood flow.

Poloxamer 188 improves neurologic outcome after hypothermic circulatory arrest.

Poloxamer 188, an amphipathic copolymer with cytoprotective properties, was investigated as a means of improving neurologic outcome after a prolonged period (150 minutes) of deep hypothermic circulatory arrest. Dogs were perfusion cooled and surface cooled to 10 degrees C, the heart was arrested for 150 minutes, and then the dogs were rewarmed and weaned from bypass. Seven dogs were treated with poloxamer 188 before and after deep hypothermic circulatory arrest. Six control dogs were treated with saline. Surviving dogs were evaluated for 1 week after deep hypothermic circulatory arrest for neurologic deficits or behavioral changes. Neurologic outcome was graded by the following system: grade 1, death within the observation period; grade 2, comatose; grade 3, holds head up; grade 4, sits up; grade 5, stands; grade 6, normal in both behavior and gait. There were no deaths in the seven poloxamer 188-treated animals versus three deaths in the six control dogs. Poloxamer 188-treated dogs also manifested significantly less neurologic dysfunction after deep hypothermic circulatory arrest than did the control group (p less than 0.003). This study shows that poloxamer 188 has a significant impact in improving neurologic outcome after exceptionally long periods of deep hypothermic circulatory arrest.

Esmolol prevents and suppresses arrhythmias during halothane anaesthesia in dogs.

The antiarrhythmic effect of esmolol, a selective beta 1 adrenoreceptor blocker, was evaluated in the presence of epinephrine induced arrhythmias in dogs (n = 6). The arrhythmogenic dose of epinephrine (ADE) during 1.2 MAC halothane in dogs was increased from 3.23 +/- 0.25 (mean +/- SD) to 30.90 +/- 3.56 micrograms.kg-1.min-1 (P less than 0.001) by the prior administration of esmolol 0.5 microgram.kg-1 bolus followed by an infusion at the rate of 150 micrograms.kg-1.min-1. Higher esmolol infusion doses of 200 micrograms.kg-1.min-1 further increased ADE to 99.0 +/- 2.92 micrograms.kg-1.min-1 (P less than 0.001). After discontinuation of esmolol and during continued halothane anaesthesia, ventricular tachycardia was induced by increasing the infusion rate of the 100 micrograms.ml-1 solution of epinephrine. In all dogs ventricular tachycardia was restored to sinus rhythm by a bolus dose of esmolol (1 microgram.kg-1). We conclude that esmolol pretreatment increases the ADE during halothane anaesthesia in dogs. Our data suggest that esmolol may be useful as an antiarrhythmic agent in the management of epinephrine-related ventricular arrhythmias during anaesthesia in man.

Cardiovascular effects of a nifedipine infusion during fentanyl-nitrous oxide anesthesia in dogs.

The hemodynamic effects of a nifedipine infusion were investigated in eight dogs given fentanyl/pancuronium/nitrous oxide/oxygen anesthesia. Nifedipine (20 micrograms/kg) was given intravenously over two minutes immediately prior to each 30-minute infusion at 2 micrograms/kg/min, 4 micrograms/kg/min, and 6 micrograms/kg/min. The range of plasma nifedipine levels obtained was 52.1 to 113.7 ng/mL. The predominant hemodynamic effects were significant reductions in systemic vascular resistance (SVR) and mean aortic pressure (MAP), accompanied by a rise in cardiac index and heart rate (HR). Administration of calcium chloride (20 mg/kg) after the nifedipine infusion had no effect on SVR or MAP, but HR was significantly reduced. Serum epinephrine and norepinephrine levels increased after the infusion of nifedipine and suggested that fentanyl did not completely overcome the sympathetic response to the profound vasodilatation. The resulting tachycardia in combination with diastolic hypotension from nifedipine could have a detrimental effect on the myocardial oxygen balance.

Nine-month evaluation of dogs after open-heart surgical removal of heartworms.

Adult heartworms were surgically removed from 4 infected dogs by use of intracardiac techniques during cardiopulmonary bypass. The number of worms removed ranged from 12 to 14 per dog. Observation for 9 months after surgery gave no clinical evidence of active adult heartworm infection, in spite of the consistent finding of circulating microfilariae during the follow-up period. There were no significant early or late postoperative complications. Results of postoperative hematologic and biochemical studies were unremarkable. At necropsy (following euthanasia, 9 months after surgery) the heart and pulmonary arteries of all dogs were free of adult heartworms; pathologic changes attributable to residual infection were not found.

Use of nonblood priming for open-heart surgery in dogs.

Three electrolyte solutions were used as priming perfusates for 1 hour of cardiopulmonary bypass in 9 dogs. Arterial blood pressure was maintained at a satisfactory level during perfusion and returned to the original ranges shortly after bypass. Measurement of various blood constituents indicated that they were constantly maintained in the normal range during the procedure. The PVC decreased sharply until the 3rd postperfusion day, then returned to the base-line values. Similar patterns were obtained for each solution, with no additional infusion being administered after bypass. All dogs recovered without complications and evidence of cerebral abnormalities was not seen. The dogs were euthanatized and necropsied 14 days after surgery and all major organs appeared normal on gross examination.