Retrograde perfusion with a sodium channel antagonist provides ischemic spinal cord protection

Background. Neuronal voltage-dependent sodium channel antagonists have been shown to provide neuroprotection in focal and global cerebral ischemic models. We hypothesized that retrograde spinal cord venous perfusion with phenytoin, a neuronal voltage-dependent sodium channel antagonist, would provide protection during prolonged spinal cord ischemia.

Methods. In a rabbit model, spinal cord ischemia was induced for 45 minutes. Six groups of animals were studied. Controls (group I, n = 8) received no intervention during aortic cross-clamping. Group II (n = 8) received systemic phenytoin (100 mg). Group III (n = 4) received systemic phenytoin (200 mg).Group IV (n = 8) received retrograde infusion of room temperature saline (22°C) only. Group V (n = 8) and group VI (n = 9) received retrograde infusion of 50 mg and 100 mg of phenytoin, respectively, (infusion rate: 0.8 mL · kg⁻¹ · min⁻¹ during the ischemic period). Mean arterial blood pressure was monitored continuously. Animals were allowed to recover for 24 hours before assessment of neurologic function using the Tarlov scale.

Results. Tarlov scores (0 = complete paraplegia, 1 = slight lower limb movement, 2 = sits with assistance, 3 = sits alone, 4 = weak hop, 5 = normal hop) were as follows (mean ± SEM): group I, 0.50 ± 0.50; group II, 0.25 ± 0.46; group IV, 1.63 ± 0.56; group V, 4.13 ± 0.23; and group VI, 4.22 ± 0.22 (p < 0.0001 V, VI versus I, II, IV by analysis of variance). No differences in mean arterial blood pressure were observed. All animals in group III became profoundly hypotensive and died before the conclusion of the 45-minute ischemic time.

Conclusions. Retrograde venous perfusion of the spinal cord with phenytoin, a voltage-sensitive sodium channel blocker, is safe and provides significant protection during prolonged spinal cord ischemia.     

Intravenous Phenylephrine Preconditioning of Cardiac Grafts From Non–Heart-Beating Donors

Background. Hypoxia and warm ischemia produce severe injury to cardiac grafts harvested from non-heart-beating donors. To potentially improve recovery of such grafts, we studied the effects of intravenous phenylephrine preconditioning.

Methods. Thirty-seven blood-perfused rabbit hearts were studied. Three groups of non-heart-beating donors underwent intravenous treatment with phenylephrine at 12.5 (n = 8), 25 (n = 7), or 50 μg/kg (n = 7) before initiation of apnea. Non-heart-beating controls (n = 8) received saline vehicle. Hypoxic cardiac arrest occurred after 6 to 12 minutes of apnea, followed by 20 minutes of warm in vivo ischemia. A 45-minute period of ex vivo reperfusion ensued. Nonischemic controls (n = 7) were perfused without antecedent hypoxia or ischemia.

Results. Phenylephrine 25 μg/kg significantly delayed the onset of hypoxic cardiac arrest compared with saline controls (9.6 ± 0.5 versus 7.7 ± 0.4 minutes; p = 0.00001), yet improved recovery of left ventricular developed pressure compared with saline controls (57.1 ± 5.3 versus 41.0 ± 3.4 mm Hg; p = 0.04). Phenylephrine 25 μg/kg also yielded a trend toward less myocardial edema than saline vehicle (p = 0.09).

Conclusions. Functional recovery of nonbeating cardiac grafts is improved by preconditioning. We provide evidence that the myocardium can be preconditioned with phenylephrine against hypoxic cardiac arrest.     

Spinal cord ischemia and reperfusion metabolism: The effect of hypothermia

Purpose: The metabolic and neurologic functional effects of regional hypothermia induced by cold (4° C) heparinized saline perfusion on spinal cord ischemia were evaluated in 35 rabbits.Methods: Spinal cord ischemia was induced for 20 minutes by infrarenal aortic occlusion in anesthetized animals. Regional spinal cord hypothermia was obtained by perfusing the lumbar arteries supplying the spinal cord through an infrarenal aortic catheter. The lumbar spinal cord was "snap frozen" in situ with liquid nitrogen and harvested immediately at the conclusion of the ischemic period or after 24 hours of normothermic reperfusion and neurologic observation. Spinal cord metabolic studies included determination of the energy charge and the intracellular concentrations of adenosine triphosphate, glucose, lactate, glutamate, and aspartate.Results: Postoperative neurologic function was normal in all but one animal treated with hypothermia, while normothermic ischemia resulted in paralysis in all animals ( p = 0.002). Spinal cord temperature during 20 minutes of ischemia and hypothermic perfusion decreased from 37.5° ± 0.43° C to 22.8° ± 0.00° C ( p = 0.0001) compared to a fall in systemic temperature from 38.8 to 36.1 ( p = 0.0001). Hypothermia reduced the decline in energy charge, adenosine triphosphate concentration and glucose concentration during ischemia but had no effect on markedly elevated levels of lactate acid. High-energy phosphates were restored after reperfusion in both normothermic and hypothermic animals and were not predictive of postoperative paraplegia. Intracellular glutamate and aspartate concentrations were unchanged during normothermic ischemia but decreased after reperfusion in all paralyzed animals. Intracellular glutamate and aspartate concentrations increased during hypothermic perfusion and remained elevated after reperfusion in animals with a normal or mildly abnormal neurologic examination result.Conclusions: We conclude that spinal cord hypothermia induced by cold heparinized saline perfusion is a simple technique that prevents paraplegia after 20 minutes of ischemia and preserves intracellular concentrations of important metabolites. (J VASC SURG 1994;19:332-40.)     

Heat shock improves recovery and provides protection against global ischemia after hypothermic storage

Background. Improved methods of donor heart preparation before preservation could allow for prolonged storage and permit remote procurement of these organs. Previous studies have shown that overexpression of heat-shock protein 72 provides protection against ischemic cardiac damage. We sought to determine whether rats subjected to heat stress with only 6-hour recovery could acquire protection to a subsequent heart storage for 12 hours at 4°C.

Methods. Three groups of animals (n = 10 each) were studied: control, sham-treated, and heat-shocked rats (whole-body hyperthermia 42°C for 15 minutes). After 12-hour cold ischemia hearts were reperfused on a Langendorff column. To confirm any differences in functional recovery, hearts were then subjected to an additional 15-minute period of warm global ischemia after which function and lactate dehydrogenase enzyme leakage were measured.

Results. Heat-shocked animals showed marked improvements compared with controls in left ventricular developed pressure (63 ± 4 mm Hg versus 44 ± 4 mm Hg, p < 0.05) heart rate × developed pressure (13,883 ± 1,174 beats per minute × mm Hg versus 8,492 ± 1,564 beats per minute × mm Hg, p < 0.05), rate of ventricular pressure increase (1,912 ± 112 mm Hg/second versus 1,215 ± 162 mm Hg/second, p < 0.005), rate of ventricular pressure decrease (1,258 ± 89 mm Hg/second versus 774 ± 106 mm Hg/second, p < 0.005). Diastolic compliance and lactate dehydrogenase release were improved in heat-shocked animals compared with controls and sham-treated animals. Differences between heat-shocked animals and control or sham-treated animals were further increased after the additional 15-minute period of warm ischemia. Western blot experiments confirmed increased heat-shock protein 72 levels in heat-shocked animals (> threefold) compared with sham-treated animals and controls.

Conclusions. Heat shock 6 hours before heart removal resulted in marked expression of heat-shock protein 72 and protected isolated rat hearts by increased functional recovery and decreased cellular necrosis after 12-hour cold ischemia in a protocol mimicking that of heart preservation for transplantation. Protection was further confirmed after an additional 15-minute period of warm ischemia.     

Sodium Nitroprusside Exacerbates Myocardial Ischemia–Reperfusion Injury

Background. The role of nitric oxide in myocardial ischemia–reperfusion is controversial. Although many studies claim that nitric oxide ameliorates reperfusion injury, others suggest that it exacerbates such injury, possibly through peroxynitrite production. These discordant results may be attributable to a dose-dependent phenomenon.

Methods. Isolated rabbit hearts sustained sequential periods of blood perfusion (20 minutes), warm ischemia (30 minutes), and reperfusion (20 minutes). During reperfusion, four groups underwent intracoronary infusion of saline solution (n = 6), or the nitric oxide donor sodium nitroprusside (100 nm/min [SNP100, n = 6], 1 nmol · L⁻¹/min⁻¹ [SNP1, n = 6], or 0.01 nmol · L⁻¹ · min⁻¹ [SNP0.01]). Left ventricular-developed pressure and oxygen consumption were measured after preischemic perfusion and reperfusion. Levels of myocardial nitrotyrosine, a marker for peroxynitrite, were measured after reperfusion with an immunoradiochemical assay.

Results. Postischemic-developed pressure and myocardial oxygen consumption were significantly higher in the saline group than all nitroprusside-reperfused groups (p < 0.01 for both parameters). However, there were no differences in either parameter between SNP100, SNP1, or SNP0.01. Nitrotyrosine levels were similar among the four groups (p = 0.43).

Conclusions. Nitroprusside exacerbates myocardial ischemia–reperfusion injury over a wide range of doses, although the mechanism does not appear to be mediated by peroxynitrite.     

Preconditioning: myocardial function and energetics during coronary hypoperfusion and reperfusion

Background. Ischemic preconditioning (IP) is gaining more acceptance as a protective method in beating heart surgery. Yet it remains controversial whether preconditioning can attenuate myocardial dysfunction during reperfusion after severe coronary hypoperfusion. We examined this issue and also the issue of whether this protection is mediated by adenosine A₁ receptors.

Methods. In isolated, blood-perfused rabbit hearts, the effects of IP (3 minutes of no flow ischemia and 8 minutes of reperfusion) during 30 minutes of coronary hypoperfusion and 60 minutes of reperfusion were investigated. In two groups (n = 8 each) with and without (control group) preconditioning, ventricular function was assessed by load-insensitive measures: slope of the end-systolic pressure–volume relation (E_max), slope of the stroke work/end-diastolic volume relation (M_w), and end-diastolic pressure–volume relation. External efficiency was calculated, and contractile efficiency was assessed using the reciprocal of the myocardial oxygen consumption–pressure–volume area relationship. To investigate the possible role of adenosine, the adenosine A₁ receptor antagonist DPCPX (2.5 μmol/L) was administered before preconditioning in a third group (n = 7).

Results. The effects of hypoperfusion on systolic function, diastolic function (dP/dt_min, end-diastolic pressure–volume relation), external efficiency, and contractile efficiency were similar in both the IP and control groups. Lactate efflux was significantly reduced after preconditioning (p = 0.02). During reperfusion, recovery of systolic function and coronary flow were significantly improved in the IP group compared with controls: aortic flow, 85% versus 63% (p = 0.01); dP/dt_max, 91% versus 67% (p = 0.001); pressure–volume area, 97% versus 68% (p = 0.01); E_max, 74% versus 62% (p = 0.03); and M_w, 94% versus 84% (p = 0.04). Release of creatine kinase was reduced in the IP group, 9.6 ± 1.3 U · 5 min⁻¹ · 100 g⁻¹ wet weight, versus controls, 12.7 ± 2.7 U · 5 min⁻¹ · 100 g⁻¹ wet weight (p = 0.04). During reperfusion, contractile efficiency (p = 0.03) and external efficiency (p = 0.02) recovered better in preconditioned than in untreated hearts. Recovery was less pronounced in the DPCPX group compared with the IP group (p, not significant).

Conclusions. The results, derived from load-insensitive measures, confirm that IP provides protection after episodes of severe hypoperfusion by attenuating systolic dysfunction without improving diastolic dysfunction and reduces the severity of anaerobic metabolism as well as ischemic injury. Contractile efficiency and external efficiency both indicate improved energetics after IP (oxygen utilization by the contractile apparatus). The protective effect, at least in part, is mediated by adenosine A₁ receptors.     

Intratracheal Surfactant Administration Preserves Airway Compliance During Lung Reperfusion

Background. Decreased airway compliance after lung transplantation has been observed with severe ischemia-reperfusion injury. Further, it has been shown that the surfactant system is impaired after lung preservation and reperfusion. We hypothesized that surfactant replacement after allograft storage could preserve airway compliance during reperfusion.

Methods. Rabbit lungs were harvested after flush with 50 mL/kg of cold saline solution. Immediate control lungs were studied with an isolated ventilation/perfusion apparatus using venous rabbit blood recirculated at 40 mL/min, room-air ventilation at 20 breaths/min, and constant airway pressure (n = 8). Twenty-four-hour control lungs were preserved at 4°C for 24 hours and then similarly studied (n = 7). Surfactant lungs underwent similar harvest and preservation for 24 hours, but received 1.5 mL/kg of intratracheal surfactant 5 minutes before reperfusion (n = 10). Airway pressure and flow were recorded continuously during 30 minutes of reperfusion. Tidal volume and airway compliance were calculated at 30 minutes.

Results. Tidal volume was 33.67 ± 0.57, 15.75 ± 5.72, and 29.83 ± 1.07 mL in the immediate control, 24-hour control, and surfactant groups, respectively (p = 0.004, surfactant versus 24-hour control). Airway compliance was 1.94 ± 0.27, 0.70 ± 0.09, and 1.46 ± 0.10 mL/mm Hg in the immediate control, 24-hour control, and surfactant groups, respectively (p = 0.002, surfactant versus 24-hour control).

Conclusions. We conclude that surfactant administration before reperfusion after 24 hours of cold storage preserves tidal volume and airway compliance in the isolated ventilated/perfused rabbit model of lung reperfusion injury.     

Surgical treatment of acute type A dissection: is rupture a risk factor?

Background. The purpose of this study was to evaluate the significance of aortic rupture on clinical outcome in patients after aortic repair for acute type A dissection.

Methods. One hundred and twenty patients underwent aortic operations with resection of the intimal tear and open distal anastomosis. Median age was 60 years (range 16 to 87); 78 were male. Thirty-six patients had only ascending aortic replacement, 82 had hemiarch repair, and 2 had the entire arch replaced. Retrograde cerebral perfusion was utilized in 66 patients (53%). Rupture defined as free blood in the pericardial space was present in 60 patients (50%). Univariate and multivariate analyses were performed to assess the risk factors for mortality and neurologic dysfunction.

Results. Overall hospital mortality rate was 24.2% ± 4.0% (± 70% confidence level) but did not differ between patients with aortic rupture or without (p = 0.83). The incidence of permanent neurologic dysfunction was 9.4% overall, 10.5% with rupture and 8.3% without rupture (p = 0.75). Multivariate analysis revealed absence of retrograde cerebral perfusion and any postoperative complication as statistically significant indicators for in-hospital mortality (p < 0.05). Overall 1- and 5-year survival was 85.3% and 33.7%; among discharged patients, survival in the nonruptured group was 89% and 37%, versus 81% and 31% in the ruptured group (p = 0.01).

Conclusions. Aortic rupture at the time of surgery does not increase the risk of hospital mortality or permanent neurologic complications in patients with acute type A dissections. However, aortic rupture at the time of surgery does influence long-term survival.     

Hypothermic retrograde venous perfusion with adenosine cools the spinal cord and reduces the risk of paraplegia after thoracic aortic clamping

OBJECTIVE: We evaluated the utility of retrograde venous perfusion to cool the spinal cord and protect neurologic function during aortic clamping. We hypothesized that hypothermic adenosine would preserve the spinal cord during ischemia. METHODS: Six swine (group I) underwent thoracic aortic occlusion for 30 minutes at normothermia. Group II animals underwent spinal cooling by retrograde perfusion of the paravertebral veins with hypothermic (4 degrees C) saline solution during aortic occlusion. The spinal cords of group III animals were cooled with a hypothermic adenosine solution in a similar fashion. Intrathecal temperature was monitored and somatosensory evoked potentials assessed the functional status of spinal pathways. RESULTS: Spinal cooling without systemic hypothermia significantly improved neurologic Tarlov scores in group III (4.8 +/- 0.2) and group II (3.8 +/- 0.4) when compared with group I scores (1.3 +/- 0.6) (P <.001). Furthermore, 5 of the 6 animals in group III displayed completely normal neurologic function, whereas only one animal in group II and no animals in group I did (P =.005). Somatosensory evoked potentials were lost 10.6 +/- 1.4 minutes after ischemia in group I. In contrast, spinal cooling caused rapid cessation of neural transmission with loss of somatosensory evoked potentials at 6.9 +/- 1.2 minutes in group II and 7.0 +/- 0.8 minutes in group III (P =.06). Somatosensory evoked potential amplitudes returned to 85% of baseline in group III and 90% of baseline in group II compared with only 10% of baseline in group I (P =.01). CONCLUSIONS: We conclude that retrograde cooling of the spinal cord is possible and protects against ischemic injury and that adenosine enhances this effect. The efficacy of this method may be at least partly attributed to a more rapid reduction in metabolic and electrical activity of the spinal cord during ischemia.     

S100β correlates with neurologic complications after aortic operation using circulatory arrest

Background. Astrocyte protein S100β is a potential serum marker for neurologic injury. The goals of this study were to determine whether elevated serum S100β correlates with neurologic complications in patients requiring hypothermic circulatory arrest (HCA) during thoracic aortic repair, and to determine the impact of retrograde cerebral perfusion (RCP) on S100β release in this setting.

Methods. Thirty-nine consecutive patients underwent thoracic aortic repairs during HCA; RCP was used in 25 patients. Serum S100β was measured preoperatively, after cardiopulmonary bypass, and 24 hours postoperatively.

Results. Neurologic complications occurred in 3 patients (8%). These patients had higher postbypass S100β levels (7.17 ± 1.01 μg/L) than those without neurologic complications (3.63 ± 2.31 μg/L, p = 0.013). Patients with S100β levels of 6.0 μg/L or more had a higher incidence of neurologic complications (3 of 7, 43%) compared with those who had levels less than 6.0 μg/L (0 of 30, p = 0.005). Retrograde cerebral perfusion did not affect S100β release.

Conclusions. Serum S100β levels of 6.0 μg/L or higher after HCA correlates with postoperative neurologic complications. Using serum S100β as a marker for brain injury, RCP does not provide improved cerebral protection over HCA alone.     

Preliminary experience with the St. Jude Medical Regent mechanical heart valve in the aortic position: early in vivo hemodynamic results

Background. The St. Jude Medical Regent is a new generation mechanical aortic valve.

Methods. Between March 2000 and July 2001, this valve was implanted in the aortic position in 40 patients (21 men; mean age 59.1 ± 9.0 years). Preoperatively, 24 patients (60%) were in New York Heart Association functional class III or IV. Eighteen patients (45%) underwent associated procedures. Mean valve size was 21.4 ± 2.4 mm. The mean duration of follow-up was 8.5 ± 4.5 months (range, 1 to 16 months).

Results. There were no operative deaths. Early complications included one reoperation for bleeding and one transient low output syndrome. Valve replacement was followed by a significant reduction in mean and peak transaortic gradients over time (p < 0.001) and analysis of variance failed to demonstrate statistical differences between valve size over time (p = not significant). A significant reduction in left ventricular hypertrophy occurred over time (p = 0.01) in all valve sizes (p = not significant between groups): baseline left ventricular mass index was 194 g/cm²; it reduced by 22 g/cm² (p = 0.006) at discharge. Left ventricular mass index decreased from 172 ± 55 g/cm² to 156 ± 44 g/cm² (p = 0.03) from discharge to 2 months. Further reductions were not significant. Relative wall thickness decreased from 0.57 ± 0.13 preoperatively to 0.42 ± 0.06 at discharge (p = 0.001), and again at 2 months (−0.2; p = not significant), and at 1 year (−0.02; p = not significant).

Conclusions. The early experience with the St. Jude Medical Regent valve has been satisfactory.     

Adenosine-enhanced ischemic preconditioning provides enhanced cardioprotection in the aged heart

Background. Recently we have reported a novel myoprotective protocol “adenosine-enhanced ischemic preconditioning” (APC), which extends and amends the protection afforded by ischemic preconditioning (IPC) by both reducing myocardial infarct size and enhancing postischemic functional recovery in the mature rabbit heart. However, the efficacy of APC in the senescent myocardium was unknown.

Methods. The efficacy of APC was investigated in senescent rabbit hearts and compared with magnesium-supplemented potassium cardioplegia (K/Mg) and IPC. Global ischemia (GI) hearts were subjected to 30 minutes of global ischemia and 120 minutes of reperfusion. Ischemic preconditioning hearts received 5 minutes of global ischemia and 5 minutes of reperfusion before global ischemia. Magnesium-supplemented potassium cardioplegia hearts received cardioplegia just before global ischemia. Adenosine-enhanced ischemic preconditioning hearts received a bolus injection of adenosine in concert with IPC. To separate the effects of adenosine from that of APC, a control group (ADO) received a bolus injection of adenosine 10 minutes before global ischemia.

Results. Infarct size was significantly decreased to 18.9% ± 2.7% with IPC (p < 0.05 versus GI); 17.0% ± 1.0% with ADO (p < 0.05 versus GI); 7.7% ± 1.3% with K/Mg (p < 0.05 versus GI, IPC, and ADO); and 2.1% ± 0.6% with APC (p < 0.05 versus GI, IPC, ADO, and K/Mg; not significant versus control). Only APC and K/Mg significantly enhanced postischemic functional recovery (not significant versus control).

Conclusions. Adenosine-enhanced ischemic preconditioning provides similar protection to K/Mg cardioplegia, significantly enhancing postischemic functional recovery and decreasing infarct size in the senescent myocardium.     

Calcitonin Gene-Related Peptide-Induced Preconditioning Improves Preservation With Cardioplegia

Background. Our recent work has shown that calcitonin gene-related peptide (CGRP) may play an important role in mediation of ischemic preconditioning. Therefore, we tested the hypothesis that CGRP-induced preconditioning protects against myocardial damage after prolonged cardioplegic arrest in isolated rat hearts.

Methods. Six groups were studied: the control, ischemic preconditioning, and CGRP-pretreated groups for both 4- and 8-hour hypothermic ischemia. All hearts were arrested using St. Thomas Hospital cardioplegia, and then reperfused with normothermic Krebs-Henseleit solution for 60 minutes after the 4- or 8-hour hypothermic ischemic period. Hearts were subjected to two cycles of 5-minute ischemia and 10-minute reperfusion in the ischemic preconditioning group. In the CGRP-pretreated group, Krebs-Henseleit solution containing CGRP (5 × 10⁻⁹ mol/L) was substituted for the ischemic period.

Results. At 30 minutes of reperfusion after 4-hour storage, left ventricular pressure (mm Hg) and its first derivative (dp/dt_max, mm Hg/s) in the control, ischemic preconditioning, and CGRP groups were 65.2 ± 5.93 and 1,170 ± 119, 94.13 ± 4.93 and 1,825 ± 145.83, and 85.47 ± 4.17 and 1,900 ± 123.13, respectively (p < 0.01). After 8-hour storage, left ventricular pressure (mm Hg) and dp/dt_max (mm Hg/s) in the same groups were 51.07 ± 5.83 and 815 ± 107.17, 83.47 ± 6.54 and 1,480 ± 120.91, and 84.8 ± 8.49 and 1,396 ± 126.16 (p < 0.01). Ischemic preconditioning and CGRP-induced preconditioning also significantly reduced the release of myocardial enzymes.

Conclusions. The present studies suggest that ischemic preconditioning protects against ischemia-reperfusion injury even after 8 hours of hypothermic preservation in isolated rat hearts, and that CGRP exerts preconditioning-like cardioprotection.     

Prevention of Reperfusion Injury by Inhaled Nitric Oxide in Lungs Harvested From Non-Heart-Beating Donors

Background. In lung transplantation using non-heart-beating donors (NHBD), the postmortem period of warm ischemia exacerbates lung ischemia-reperfusion injury. We hypothesized that inhaled nitric oxide (NO) would reduce ischemia-reperfusion injury, and thus ameliorate the viability of the lung graft.

Methods. A blood-perfused, isolated rat lung model was used. Lungs were flushed and harvested from non-heart-beating donors after 30 minutes of in situ warm ischemia. The lung was then stored for 2 hours at 4°C. Inhaled NO at 30 ppm was given either during the period of warm ischemia, during reperfusion, or during both periods. Lung ischemia-reperfusion injury was assessed after 1 hour of reperfusion by measuring pulmonary vascular resistance, coefficient of filtration, wet-to-dry lung weight ratio, and myeloperoxidase activity.

Results. A severe IR injury occurred in lungs undergoing ischemia and reperfusion without NO as evidenced by high values of pulmonary vascular resistance (6.83 ± 0.36 mm Hg · mL⁻¹ · min⁻¹), coefficient of filtration (3.02 ± 0.35 mL · min⁻¹ · cm H₂O⁻¹ · 100 g⁻¹), and wet-to-dry lung weight ratio (8.07 ± 0.45). Lower values (respectively, 3.31 ± 0.44 mm Hg · mL⁻¹ · min⁻¹, 1.49 ± 0.34 mL · min⁻¹ · cm H₂O⁻¹ · 100 g⁻¹, and 7.44 ± 0.43) were observed when lungs were ventilated with NO during ischemia. Lung function was further improved when NO was given during reperfusion only. All measured variables, including myeloperoxidase activity were significantly improved when NO was given during both ischemia and reperfusion. Myeloperoxidase activity was significantly correlated with coefficient of filtration (r = 0.465; p < 0.05).

Conclusions. These data suggest that inhaled NO significantly reduces ischemia-reperfusion injury in lungs harvested from non-heart-beating donors. This effect might be mediated by inhibition of neutrophil sequestration in the reperfused lung.     

Intraaortic Balloon Counterpulsation Improves Right Ventricular Failure Resulting From Pressure Overload

Background. Right ventricular (RV) dysfunction is common after heart transplantation, and myocardial ischemia is considered to be a significant contributor. We studied whether intraaortic balloon counterpulsation would improve cardiac function using a model of acute RV pressure overload.

Methods. In 10 anesthetized sheep, RV failure was induced using a pulmonary artery constrictor. Baseline measurements included mean systemic blood pressure, RV peak systolic pressure, cardiac index, and RV ejection fraction. Myocardial and organ perfusion were measured using radioactive microspheres.

Results. After pulmonary artery constriction, there was an increase in RV peak systolic pressure (32 ± 2 to 60 ± 3 mm Hg; p < 0.01) and a decrease in mean systemic blood pressure (68 ± 4 to 49 ± 2 mm Hg; p < 0.01), RV ejection fraction (0.51 ± 0.04 to 0.16 ± 0.02; p < 0.01), and cardiac index (2.48 ± 0.04 to 1.02 ± 0.11; p < 0.01). Blood flow to the RV did not change significantly, but there was a significant reduction in blood flow to the left ventricle. The initiation of intraaortic balloon counterpulsation (1:1) using a 40-mL intraaortic balloon inserted through the left femoral artery resulted in an increase in mean systemic blood pressure (49 ± 2 to 61 ± 3 mm Hg; p < 0.01), cardiac index (1.02 ± 0.11 to 1.45 ± 0.14; p < 0.05), RV ejection fraction (0.16 ± 0.02 to 0.23 ± 0.02; p < 0.01), and blood flow to the left ventricle.

Conclusions. In a model of right heart failure, the institution of intraaortic balloon counterpulsation caused a significant improvement in cardiac function. Although RV ischemia was not demonstrated, the augmentation of left coronary artery blood flow by intraaortic balloon counterpulsation and subsequent improvement in left ventricular function suggest that left ventricular ischemia contributes to RV dysfunction, presumably through a ventricular interdependence mechanism. Therefore, study of the safety and efficacy of intraaortic balloon counterpulsation in the management of patients with acute right heart dysfunction is warranted.     

Prospective randomized neurocognitive and S-100 study of hypothermic circulatory arrest, retrograde brain perfusion, and antegrade brain perfusion for aortic arch operations

Background. To determine the optimal method of brain protection during deep hypothermic circulatory arrest (DHCA) for arch repair.

Methods. Of 139 potential aortic arch repairs (denominator), we randomized 30 patients to either DHCA alone (n = 10), DHCA plus retrograde brain perfusion (RBP) (n = 10), or antegrade perfusion (ANTE) (n = 10); a further 5 coronary bypass (CAB) patients were controls. Fifty-one neurocognitive subscores were obtained for each patient at each of four intervals: preoperatively, 3 to 6 days postoperatively, 2 to 3 weeks postoperatively, and 6 months postoperatively. Intraoperative and postoperative S-100 blood levels and electroencephalograms were also obtained.

Results. For the denominator, the 30-day and hospital survival rate was 97.8% (136 of 139) and the stroke rate 2.8% (4 of 139). For the randomized patients, the survival rate was 100% and no patient suffered a stroke or seizure. Circulatory arrest (CA) times were not different (DHCA:RBP:ANTE) for 11 total arch repairs (including 6 elephant trunk; mean, 41.4 minutes; standard deviation, 15). Hemi-arch repairs (n = 17) were quickest with DHCA (mean 10.0 minutes; standard deviation, 3.6; p = 0.011) and longest with ANTE (mean 23.8 minutes; standard deviation, 10.28; p = 0.004). Of the patients, 96% had clinical neurocognitive impairment at 3 to 6 days, but by 2 to 3 weeks only 9% had a residual new deficit (1 DHCA, 1 RBP, 1 ANTE), and by 6 months these 3 patients had recovered. Comparison of postoperative mean scores showed the DHCA group did better than RBP patients in 5 of 7 significantly different (p < 0.05) scores and versus 9 of 9 ANTE patients. There were no S-100 level differences between CA groups, but levels were significantly higher versus the CAB controls, particularly at the end of bypass (p < 0.0001); however, these may have been influenced by other variables such as greater pump time, cardiotomy use, and postoperative autotransfusion. Circulatory arrest (p = 0.01) and pump time (p = 0.057) correlated with peak S-100 levels.

Conclusions. The results of hypothermic arrest have improved; however, there is no neurocognitive advantage with RBP or ANTE. Nevertheless, retrograde brain perfusion may, in a larger study, potentially reduce the risk of strokes related to embolic material. S-100 levels may be artificial. In patients with severe atheroma or high risk for embolic strokes, we use a combination of retrograde and antegrade perfusion on a selective basis.     

Efficacy of intracoronary versus intravenous FGF-2 in a pig model of chronic myocardial ischemia

Background. Therapeutic angiogenesis in ischemic myocardium has been shown to be a feasible and effective strategy to improve regional blood flow and myocardial function. However, the optimal mode of growth factor administration still needs to be established.

Methods. Using a pig model of chronic myocardial ischemia, we evaluated the efficacy of intravenous and intracoronary infusion of FGF-2 at 2 and 6 μg/kg compared with a vehicle control. Improvement in myocardial perfusion and function was assessed by angiography, colored microspheres, and function and perfusion magnetic resonance imaging.

Results. Intracoronary 6-μg/kg FGF-2 increased angiographic collaterals (p = 0.046) and increased regional blood flow to the ischemic area from 0.36 ± 0.07 to 0.59 ± 0.08 mL/min/g at stress (vs control, p = 0.032). Also, after 6 μg/kg intracoronary FGF-2, ejection fraction, regional wall motion, and thickening improved significantly by 9.9% ± 1.9%, 126% ± 39%, and 13.8% ± 3.6%, respectively. Intravenous FGF-2 and intracoronary 2 μg/kg FGF-2 were ineffective.

Conclusions. A single 6-μg/kg intracoronary treatment with FGF-2 resulted in significant improvement in collateralization and regional and global function of chronically ischemic myocardium. Single intravenous infusion of FGF-2 was not effective in this model.     

Ministernotomy versus median sternotomy for aortic valve replacement: a prospective, randomized study

Background. Minimally invasive aortic valve replacement reduces surgical trauma and, supposedly, postoperative pain, blood loss, and length of stay. A prospective, randomized study was designed to prove these theoretical advantages.

Methods. Forty patients undergoing isolated, elective aortic valve replacement were randomized into two equal groups. Patients in group M underwent aortic valve replacement through a ministernotomy (reversed or reversed ). In group S, a median sternotomy was used. The anesthetic and surgical protocol was identical for both groups. Pain was evaluated on a daily basis. Pulmonary function tests were performed preoperatively and before hospital discharge in all patients.

Results. There were two deaths in each group. Cross-clamp time was longer in group M: 70 ± 19 minutes versus 51 ± 13 minutes in group S (p = 0.005). There were no statistically significant differences between groups M and S in pump time (95 ± 20 minutes versus 83 ± 19 minutes), extubation time (9.9 hours in both groups), chest drainage (479 ± 274 mL/ 24 hours versus 355 ± 159 mL/ 24 hours), transfusion requirements (27% in both groups), pain evaluation (1.34 ± 1.3 versus 2.15 ± 1.5), length of stay (6.2 ± 2.3 days versus 6.3 ± 2.5 days), and cosmetic appraisal. Forced vital capacity decreased 26% from preoperative reference values in group M and 33% in group S (p = not significant). Forced expiratory volume in 1 second decreased 22% and 35%, respectively (p = not significant).

Conclusions. This study has failed to prove the theoretical advantages of minimally invasive aortic valve replacement. With this technique, cross-clamp time is longer than with a median sternotomy.     

Aprotinin reduces injury of the spinal cord in transient ischemia

Objective: The protective effect of aprotinin, which is a protease inhibitor, was assessed in a rabbit spinal cord ischemia model. Design: Randomized, controlled, prospective study. Setting: University research laboratory. Subjects: New Zealand white rabbits (36) of both sexes. Methods: In 24 animals, ischemia was induced with midline laparotomy and clamping the aorta just distal to left renal artery and proximal to aortic bifurcation for 20 min. Aprotinin was given 30 000 KIU as a short intravenous injection after anesthesia, and was followed by 10 000 KIU/h by continuous infusion in group 1 (n=12). Similar volume of saline solution was used in control group of animals (group 2, n=12). Group 3 of animals (sham group, n=12) were anesthetized and subjected to laparotomy without aortic occlusion. Physiological parameters and somatosensory evoked-potentials (SEP) were monitored in animals before ischemia, during ischemia and in the first 60 min of reperfusion. Their neurological outcome was clinically evaluated up to 48 h postischemia. Their motor function was scored, and the intergroup differences were compared. The animals were sacrificed after two days of postischemia. Their spinal cord, abdominal aorta, and its branches were processed for histopathological examination. Results: In group 3, SEP amplitudes did not change during the procedures, and all animals recovered without neurologic deficits. At the end of ischemic period, the average amplitude was reduced to 53±7% of the baseline in all ischemic animals. This was followed by a gradual return to 89±8 and 81±13% of the initial amplitude after 60 min of reperfusion in group 1 and group 2 correspondingly (P>0.05). The average motor function score was significantly higher in group 1 than group 2 at 24 and 48 h after the ischemic insult (P<0.05). Histological observations were clearly correlated with the neurological findings. Conclusion: The results suggest that aprotinin reduces spinal cord injury and preserves neurologic function in transient spinal cord ischemia in rabbits.     

Cardiotomy Suction: A Major Source of Brain Lipid Emboli During Cardiopulmonary Bypass

Background. Brain injury remains a significant problem in patients undergoing cardiac surgery assisted by cardiopulmonary bypass (CPB). Autopsy brain specimens of patients after cardiac operations with CPB reveal numerous acellular lipid deposits (10 to 70 μm) in the microvasculature. We hypothesize that these small capillary and arterial dilatations result from a diffuse inflammatory response to CPB or from emboli delivered by the bypass circuit. This study was undertaken to determine which aspect of CPB is most clearly associated with these dilatations.

Methods. Thirteen dogs were studied in four groups: group I (n = 3), right-heart CPB; group II (n = 2), lower-extremity CPB; group III (n = 3), hypothermic CPB; and group IV (n = 5), hypothermic CPB with cardiotomy suction. All dogs in all groups were maintained on CPB for 60 minutes and then euthanized. Brain specimens were harvested, fixed in ethanol, embedded in celloidin, and stained with the alkaline phosphate histochemical technique so that dilatations could be counted.

Results. All dogs completed the protocol. The mean density of dilatations per square centimeter for each group was as follows: group I, 1.77 ± 0.77; group II, 4.17 ± 1.65; group III, 4.54 ± 1.69; and group IV, 46.5 ± 14.5. In group IV (cardiotomy suction), dilatation density was significantly higher than in group III (hypothermic cardiopulmonary bypass) (p = 0.04) and all other groups (p = 0.04).

Conclusions. Blood aspirated from the surgical field and subsequently reinfused into dogs undergoing CPB produces a greater density of small capillary and arterial dilatations than CPB without cardiotomy suction, presumably because of lipid microembolization.