Head injury and hemorrhagic shock: studies of the blood brain barrier and intracranial pressure after resuscitation with normal saline solution, 3% saline solution, and dextran-40

The effect of fluid resuscitation from hemorrhagic shock on cerebral edema, intracranial pressure (ICP), and blood brain barrier function was investigated in the presence of a simulated head injury. Beagle dogs were anesthetized and ICP was measured via a right subarachnoid bolt while a contralateral epidural balloon was inflated in the left hemicranium to mimic a closed head injury. Forty percent of the dogs' blood was shed and the shock state was maintained for 1 hour. Resuscitation was initiated with shed blood and a volume of either normal saline solution (NS, n = 5), 10% dextran-40 (D-40, n = 6), or hypertonic (3%) saline solution (HS, n = 6) equal to the amount of shed blood. Evans blue solution was infused intravenously, and intravascular volume was then maintained with normal saline solution. Control (n = 5) dogs did not undergo shock, but received equivalent volumes of normal saline solution and Evans blue solution. The dogs were killed after 2 hours of resuscitation, and the brains were removed, weighed, and fixed in formalin. The average intracranial pressure value after epidural balloon inflation was 18.6 +/- 0.80 mm Hg and decreased equally in all groups during the shock period, averaging 10.8 +/- 1.24 mm Hg at the end of the shock period. Fluid resuscitation markedly elevated ICP in the NS and D-40 groups, reaching maximal values of 46.6 +/- 12.11 mm Hg and 45.3 +/- 28.95 mm Hg, respectively. Maximal ICP values in control and HS groups measured 21.8 +/- 1.36 mm Hg and 15.8 +/- 2.04 mm Hg, respectively (p less than 0.25 for HS versus NS control). Wet brain weights were significantly less in the HS group compared with either NS or D-40 groups (p less than 0.05). Coronal sections of fixed HS brains showed deep cortical Evans blue staining on the side of balloon injury. Therefore, in the presence of an intracranial mass lesion, resuscitation with hypertonic (3%) saline solution is accompanied by lower ICP values and less cerebral edema than is isotonic saline or colloid resuscitation. Blood brain barrier function is not restored by hypertonic saline solution resuscitation.     

The stretched ventricle. Myocardial creep and contractile dysfunction after acute nonischemic ventricular distention.

The hypothesis that nonischemic distention of the arrested, flaccid ventricle causes myocardial creep and reduces ventricular contractile force was tested in 16 sheep. Left ventricular volume was calculated from ultrasonic dimension transducers spanning left ventricular major and minor axes and left ventricular wall thickness. Changes in left ventricular volume were plotted against left ventricular pressure, with and without temporary occlusion of both venae cavae before and after nonischemic distention of the continuously perfused, flaccid nonbeating left ventricle arrested with oxygenated, normothermic blood-potassium perfusate. During 12 minutes of cardiac arrest, an apical balloon progressively distended the left ventricle to a peak pressure of 40 mm Hg in 11 sheep using a protocol designed to prevent subendocardial ischemia or mechanical injury. Coronary sinus lactate measurements and myocardial distribution of microspheres confirmed the absence of ischemia in 16 animals. In five control sheep the balloon was inserted but not inflated. Left ventricular volume at zero pressure increased from 5.9 +/- 3.5 to 9.5 +/- 4.4 ml (p < 0.05) after balloon inflation and did not change in the control animals. After maximum distention of the balloon, static left ventricular volumes at identical pressures were significantly greater. After passive distention, the slope of the end-systolic pressure-volume relationship, a measure of contractility, decreased significantly (p < 0.05) from 7.1 +/- 2.8 to 3.5 +/- 1.8 mm Hg/ml and did not change in the control group. Passive distention ("stretching") of the nonischemic flaccid left ventricle thus causes myocardial creep and reduces ventricular contractility.     

Cerebral perfusion during canine hypothermic cardiopulmonary bypass: effect of arterial carbon dioxide tension

Cerebral blood flow (radioactive microspheres), intracranial pressure (subdural bolt), and retinal histopathology were examined in 20 dogs undergoing 150 minutes of hypothermic (28 degrees C) cardiopulmonary bypass to compare alpha-stat (arterial carbon dioxide tension, 40 +/- 1 mm Hg; n = 10) and pH-stat (arterial carbon dioxide tension, 61 +/- 1 mm Hg; n = 10) techniques of arterial carbon dioxide tension management. Pump flow (80 mL.kg-1.min-1), mean aortic pressure (78 +/- 2 mm Hg), and hemoglobin level (87 +/- 3 g/L [8.7 +/- 0.3 g/dL]) were maintained constant. During bypass, intracranial pressure progressively increased in the alpha-stat group from 6.0 +/- 1.0 to 13.9 +/- 1.8 mm Hg (p less than 0.05) and in the pH-stat group from 7.7 +/- 1.1 to 14.7 +/- 1.4 mm Hg (p less than 0.05), although there was no evidence of loss of intracranial compliance or intracranial edema formation as assessed by brain water content. With cooling, cerebral blood flow decreased by 56% to 62% in the alpha-stat group (p less than 0.05) and by 48% to 56% in the pH-stat group (p less than 0.05). However, 30 minutes after rewarming to 37 degrees C, cerebral blood flow in both groups failed to increase and remained significantly depressed compared with baseline values. Both groups showed similar amounts of ischemic retinal damage, with degeneration of bipolar cells found in the inner nuclear layer in 67% of animals. We conclude that, independent of the arterial carbon dioxide tension management technique, (1) cerebral perfusion decreased comparably during prolonged hypothermic bypass, (2) intracranial pressure increases progressively, (3) ischemic damage to retinal cells occurs despite maintenance of aortic pressure and flow, and (4) a significant reduction in cerebral perfusion persists after rewarming.     

Effects of left ventricular venting and distention during heterogenous distribution of cardioplegic solution

The effects of left ventricular venting and distention on myocardial protection during heterogenous distribution of cardioplegic solution remain undefined. This study was undertaken to determine if left ventricular venting enhances and distention impairs myocardial cooling and recovery of global and regional left ventricular function. Twenty-one pigs were placed on cardiopulmonary bypass and subjected to 80 minutes of ischemic arrest with the mid-left anterior descending artery occluded. Hearts were protected with multidose potassium (25 mEq/L) crystalloid cardioplegic solution supplemented with topical (4 degrees C) and systemic (28 degrees C) hypothermia. During arrest, the left ventricle was vented in seven pigs, seven pigs were not vented, and seven others had systemic pump blood infused into the left ventricle to maintain an end-diastolic pressure of 15 mm Hg. Parameters measured included left ventricular temperature, stroke work index, compliance (end-diastolic pressure-end-diastolic volume curves) and wall motion scores (two-dimensional echocardiography). Distended hearts had the lowest mean left ventricular temperature beyond the left anterior descending arterial occlusion (10.1 degrees +/- 1.8 degrees C distended [p less than 0.025 from vented and nonvented groups] versus 14.2 degrees +/- 0.7 degrees C vented versus 15.5 degrees +/- 1.2 degrees C nonvented), the highest postischemic stroke work index (0.78 +/- 0.09 gm-m/kg distended versus 0.62 +/- 0.07 gm-m/kg vented versus 0.66 +/- 0.07 gm-m/kg nonvented at end-diastolic pressure = 10 mm Hg), and the best wall motion scores (0.7 +/- 0.04 distended [p less than 0.025 from vented and nonvented groups] versus 5.5 +/- 1.80 vented versus 4.8 +/- 1.20 nonvented). Postischemic end-diastolic pressure-end-diastolic volume curves were unchanged from preischemic values in each group. We conclude that during heterogenous cardioplegic arrest, left ventricular venting offers no additional myocardial protection and may negate the beneficial effects of moderate (end-diastolic pressure = 15 mm Hg) left ventricular distention.     

Vasoreactivity of arterial grafts in the patient with diabetes mellitus: investigations on internal thoracic artery and radial artery conduits.

OBJECTIVE: Arterial revascularization with either internal thoracic artery (ITA) or radial artery (RA) appears to be particularly attractive in diabetic patients. Previous investigations have shown that endothelial dysfunction and artherosclerosis are seen more often in these patients. The aim of this study was to compare the vasoreactive properties of ITA and RA grafts in diabetic and non-diabetic patients. METHODS: Arterial rings were harvested from 57 patients who underwent complete arterial revascularization. The patients were divided into a non-diabetic group (I: n = 30) and patients with diabetes mellitus (II: n = 27). Arterial rings of the ITA (I: n = 30; II: n = 27) and RA (I: n = 28; II: n = 19) were mounted on a strain gauge in oxygenated, normothermic Krebs's--Henseleit solution at optimal resting tension. With KCL (80 mM) serving as the control, assessment of force of contraction (norepinephrine), endothelium-dependent relaxation (acetylcholine) and smooth muscle-dependent relaxation (glyceroltrinitrate) were obtained. RESULTS: After KCL, the RA showed a trend to lower maximum contraction forces in diabetics (I: 76 +/- 25 mN; II: 69 +/- 29 mN), which was pronounced in patients with diabetes of more than 10 years duration (55 +/- 23 mN; P = 0.1). Maximum contraction force of the ITA was similar in both groups (I: 41 +/- 20 mN; II: 34 +/- 19 mN) and not influenced by the duration of diabetes. The two groups showed no significant differences of the relative vasoconstriction after norepinephrine in RA (I: 53 +/- 18%; II: 61 +/- 19%) and ITA rings (I: 70 +/- 23%; II: 69 +/- 25%). Also, endothelium-dependent relaxation with acetylcholine in RA (I: 53 +/- 14%; II: 57 +/- 16%) and ITA rings (I: 42 +/- 17%; II: 44 +/- 20%), and smooth muscle relaxation with glyceroltrinitrate of RA (I: 72 +/- 8%; II: 73 +/- 12%) and ITA rings (I: 64 +/- 12%; II: 58 +/- 20%) was comparable in both groups. No influence of duration of the diabetic disease was noted. CONCLUSIONS: Although RA rings of patients with a long duration of diabetes have decreased maximum contraction forces, their relative vasoconstriction after norepinephrine, endothelium-dependent relaxation and smooth muscle relaxation was similar to non-diabetic patients. We thus conclude that the RA is an adequate arterial conduit in the patient with diabetes mellitus.     

Functional assessment of skeletal muscle ventricles after pumping for up to four years in circulation

BACKGROUND: The successful treatment of cardiac failure by heart transplantation is severely limited by the shortage of donor organs, and alternative surgical approaches are needed. An experimental approach that holds considerable promise is the skeletal muscle ventricle (SMV), an auxiliary blood pump formed from a pedicled graft of latissimus dorsi muscle and connected to the circulation in a cardiac assist configuration. Adaptive transformation, or conditioning, by electrical stimulation enables the skeletal muscle to perform a significant proportion of cardiac work indefinitely without fatigue. METHODS: In 10 dogs, SMVs were constructed from the latissimus dorsi muscle, lined internally with pericardium, and conditioned by electrical stimulation to induce fatigue resistant properties. The SMVs were connected to the descending thoracic aorta via two 12-mm Gore-Tex conduits and the aorta was ligated between the two grafts. The SMV was stimulated to contract during the diastolic phase of alternate cardiac cycles. The animals were monitored at regular intervals. RESULTS: At initial hemodynamic assessment, SMV contraction augmented mean diastolic blood pressure by 24.6% (from 61 +/- 7 to 76 +/- 9 mm Hg). Presystolic pressure was reduced by 15% (from 60 +/- 8 to 51 +/- 7 mm Hg) after an assisted beat. Four animals died early, 1 from a presumed arrhythmia, and 3 during propranolol-induced hypotension. The other 6 animals survived for 273, 596, 672, 779, 969, 1,081, and 1,510 days. Diastolic augmentation was 27.4% at 1 year (93 +/- 9 vs 73 +/- 6 mm Hg; n = 5), 34.7% at 2 years (85 +/- 6 vs 63 +/- 7 mm Hg; n = 3), 21.2% (89 +/- 10 vs 73 +/- 8 mm Hg; n = 2) at 3 years, and 34.5% (78 vs 58 mm Hg; n = 1) after 4 years in circulation. After 4 years, the isolated SMV was able to maintain a pressure of over 80 mm Hg while ejecting fluid at 20 mL/s. No animal showed evidence of SMV rupture or thromboembolism. CONCLUSIONS: The SMVs in this study provided effective and stable hemodynamic assistance over an extended period of time. There was no evidence that the working pattern imposed on the muscular wall of the SMV compromised its viability. Areas of fibrofatty degeneration were suggestive of early damage that future protocols should seek to minimize.     

Hypercapnia improves tissue oxygenation in morbidly obese surgical patients

Risk of wound infection is increased in morbidly obese surgical patients, in part because a major determinant of wound infection risk, tissue oxygenation, is marginal. Unlike in lean patients, supplemental inspired oxygen (Fio2) only slightly improves tissue oxygenation in obese patients. Mild hypercapnia improves tissue oxygenation in lean patients but has not been evaluated in obese patients. We thus tested the hypothesis that mild hypercapnia markedly improves tissue oxygenation in morbidly obese patients given Fio2 80% during major abdominal surgery. Thirty obese patients (body mass index 61.5 +/- 17 kg/m2) scheduled for open gastric bypass were randomly assigned to normocapnia (n = 15, end-tidal Pco2 35 mm Hg) or hypercapnia (n = 15, end-tidal Pco2 50 mm Hg); Fio2 was 80%. Anesthetic management and other confounding factors were controlled. Tissue oxygen tension was measured subcutaneously at the upper arm using a polarographic probe in a silastic tonometer. Demographic characteristics, cardiovascular measurements, and Pao2 (222 +/- 48 versus 230 +/- 68 mm Hg in normocapnic versus hypercapnic; mean +/- sd; P = 0.705) were comparable in the groups. Tissue oxygen tension, however, was greater in hypercapnic than in normocapnic patients (78 +/- 31 versus 56 +/- 13 mm Hg; P = 0.029). Mild hypercapnia increased tissue oxygenation by an amount believed to be clinically important and could potentially reduce the risk of surgical wound infection in morbidly obese patients.     

Myointimal thickening in experimental vein grafts is dependent on wall tension.

This study examines the relative contributions of intraluminal pressure, blood flow, wall tension, and shear stress to the development of myointimal thickening in experimental vein grafts. To study these different hemodynamic parameters, several experimental models were created in 30 New Zealand White rabbits separated into six groups: common carotid interposition vein grafts harvested at 4 weeks (VG-4) or 12 weeks (VG-12), common carotid-linguofacial vein arteriovenous fistulas harvested at 4 weeks (AVF-4) or 12 weeks (AVF-12), AVFs with partial outflow obstruction harvested at 4 weeks (AVFobs), and combination VG-AVFs in series harvested at 4 weeks (VGAVF). Blood pressure and flow in the graft or vein were measured by use of a transducer-tipped pressure catheter and electromagnetic flow meter. At harvest, veins were perfusion-fixed and proximal, middle, and distal sections were subjected to computerized morphometric analysis. Vein grafts were characterized by a high mean pressure (VG-4, 51 +/- 4; VG-12, 62 +/- 3 mm Hg), low mean flow (VG-4, 17 +/- 1; VG-12, 16 +/- 4 ml/min), large luminal area (VG-4, 19.7 +/- 2.4; VG-12, 19.3 +/- 3.9 mm2), high wall tension (VG-4, 17.0 +/- 1.5; VG-12, 19.5 +/- 2.4 x 10(3) dyne/cm), low shear stress (VG-4, 0.75 +/- 0.13; VG-12, 0.96 +/- 0.38 dyne/cm2), and a high degree of myointimal thickening (VG-4, 5.89 +/- 0.90; VG-12, 4.72 +/- 0.83 mm2). Arteriovenous fistulas were characterized by a low mean pressure (AVF-4, 5 +/- 1, AVF-12, 6 +/- 2 mm Hg), elevated blood flow (AVF-4, 82 +/- 16; AVF-12, 82 +/- 17 ml/min), small luminal area (AVF-4, 2.43 +/- 0.58; AVF-12, 7.14 +/- 2.68), low wall tension (AVF-4, 0.62 +/- 0.19; AVF-12, 0.89 +/- 0.24 x 10(3) dyne/cm), elevated shear stress (AVF-4, 108 +/- 32; AVF-12, 71 +/- 50 dyne/cm2), and decreased myointimal area (AVF-4, 1.18 +/- 0.26; AVF-12, 1.90 +/- 0.55 mm2). The addition of outflow obstruction to AVFs (AVFobs) resulted in elevated pressure (48 +/- 2 mm Hg), decreased flow (17 +/- 4 ml/min), larger luminal area (8.71 +/- 2.31 mm2), elevated wall tension (10.3 +/- 1.7 x 10(3) dyne/cm), and a degree of myointimal thickening approaching that of vein grafts (3.79 +/- 0.66 mm2).(ABSTRACT TRUNCATED AT 400 WORDS)     

Association of artery wall hypoxia and cellular proliferation at a vascular anastomosis

BACKGROUND: We hypothesize that arterial wall hypoxia incites the pathologic formation of intimal hyperplasia at an artery anastomosis. We have determined from previous studies performed in our laboratory, the oxygen tension profiles of the artery wall at various times after vascular anastomosis. The purpose of this study is to determine the rate of cellular proliferation at an artery anastomosis when the artery wall is most hypoxic. MATERIALS AND METHODS: Expanded polytetrafluoroethylene (ePTFE) grafts were placed end to end in the infrarenal aorta of 27 New Zealand white rabbits. The anastomotic aortic wall oxygen (O(2)) tensions were measured with an O(2) microelectrode in rabbits 0, 7, 14, 28, and 42 days after surgery. O(2) tensions were also measured in 4 control rabbits for comparison. 5-Bromo-2'-deoxyuridine (BrDU) was injected intraperitoneally 24 h prior to rabbit sacrifice. After O(2) tension measurements, the rabbits were sacrificed and the aortic grafts were harvested. Bioquant morphometrics was used to measure cells with BrDU counterstaining and intimal thickness in 17 rabbits: in control (n = 4), Day 0 (n = 4), 7 (n = 5), and 42 (n = 4). Student's t test was used to compare O(2) tensions, cellular proliferation, and intimal hyperplasia between days. RESULTS: The pO(2) levels at the outer layers of the aorta, 1 mm distal to the distal aortic graft anastomosis, were 61.0 +/- 2 (+/-SE) mm Hg for controls, 19.8 +/- 1 mm Hg for Day 7 (P < 0.0001), 19.0 +/- 1 mm Hg for Day 14, 39.2 +/- 1 mm Hg for Day 28, and 58.5 +/- 1 mm Hg for Day 42 aortic grafts. BrDU-staining ratios in the intima were significantly higher in the Day 7 aortic grafts, 28.6 +/- 3%, versus BrDU-staining ratio, 1.4 +/- 1%, in Day 42 aortic grafts (P < 0.0002). CONCLUSIONS: Cellular proliferation is highest at Day 7 when the artery wall is most hypoxic and returns to baseline as O(2) tensions normalize.     

The effect of intraoperative ischemia on the recovery of contractile function after free muscle transfer

Isometric contractile function was studied after recovery in free, vascularized muscle transfer subjected to graded periods of intraoperative ischemia. Fifteen dogs had orthotopic replantation of their left gracilis muscles, with intraoperative ischemia times grouped as 0 (n = 3), 1 to 2 (n = 3), 2 to 3 (n = 4), or 3 to 4 (n = 5) hours. After recovery (mean 61.8 weeks), isometric twitch and tetanic tension and fatigue measurements were made in the replants and in the contralateral, control gracilis. On the average, replants were found to produce significantly less twitch (0.32 +/- 0.13 versus 0.49 +/- 0.24 N/g) and 75 Hz tetanic tension (2.2 +/- 0.9 versus 3.4 +/- 0.5 N/g) than controls. However, in several individual replants, 100% of control maximal tetanic tension was observed. Intraoperative ischemia time of up to 4 hours was not correlated with functional return. It is concluded that (1) full recovery is possible after free muscle transfer; (2) intraoperative ischemia, if less than 4 hours long, is not the primary determinant of functional recovery; and (3) factors besides intraoperative ischemia must be operative in producing the variability in recovery seen in this setting.     

Intraoperative trauma to human saphenous veins: scanning electron microscopic comparison of preparation techniques

To determine optimal preparation techniques for human saphenous veins, a scanning electron microscopic comparison was made of the effects of variations in solutions, temperatures, and distention pressures on human vein morphology. Segments of saphenous veins obtained from 20 patients undergoing myocardial revascularization were divided into five groups of 5 veins each.Group 1 segments (controls) were immediately distended and perfusion-fixed with glutaraldehyde at 30 mm Hg to simulate in vivo saphenous vein hydrostatic pressure. Segments comprising Groups 2 and 3 were placed in heparinized normal saline solution at 28°C for one hour and then distended to either 100 mm Hg (Group 2) or 300 mm Hg (Group 3). Segments making up Groups 4 and 5 were immersed in heparinized blood for one hour at either 28°C (Group 4) or 4°C (Group 5), and then distended to 100 mm Hg. Except for controls, which were fixed as described, all other groups of vein specimens were perfusion-fixed at 100 mm Hg to simulate in vivo arterial pressure.Control veins showed focal intimal fractures with minimal endothelial cell loss due to harvesting manipulation. Groups 2 and 3 had marked endothelial loss, which led to exposure of basement membrane, collagen fibrils, and smooth muscle cells and was associated with intimal and medial edema. Veins prepared with blood appeared similar to controls, showing focal endothelial cell loss, but preservation of intimal and medial structure. Changes were less marked in Group 5 than in Group 4. We conclude that human saphenous veins are best preserved by immersion in cold blood and distention to a pressure of 100 mm Hg or less.     

Tourniquet at 50 mm Hg followed by intravenous lidocaine diminishes hand pain associated with propofol injection.

We evaluated the efficacy of intravenous lidocaine, with and without a tourniquet, to decrease the intensity of pain during intravenous propofol injection in 82 patients undergoing general anesthesia. Patients in group A (n = 20) received propofol (2 mg/kg IV); patients in group B (n = 22) received 2% lidocaine (100 mg IV) followed 1 min later by propofol (2 mg/kg). Patients in group C (n = 21, saline placebo) and D (n = 19, 2% lidocaine) had an arm tourniquet inflated to 50 mm Hg applied for 1 min after gravity drainage of venous blood. The intensity of pain along the forearm was marked on a 0-100-mm visual analogue scale. Pain intensity was less in group B (21 +/- 19 mm) than in group A (75 +/- 28 mm; P less than 0.05). Pain intensity was significantly less in group D (1 +/- 2 mm) compared with group B (21 +/- 19 mm; P less than 0.001). We conclude that intravenous lidocaine before propofol injection attenuates the painful response; whereas, lidocaine administered after a tourniquet inflated to 50 mm Hg for 1 min virtually abolishes the pain associated with intravenous propofol.     

Changes in left ventricular systolic wall stress during biventricular circulatory assistance

Extracorporeal membrane oxygenation (ECMO) reduces the systolic stress integral (SSI) in the normal left ventricle. We tested the hypothesis that the SSI does not decrease in poorly contracting, dilated, ejecting hearts during ECMO. In 14 sheep, four pairs of ultrasonic crystals measured changes in left ventricular (LV) wall thickness and three LV diameters. Volume calculations were validated by balloon distention of the ventricles after death (slope = 0.85; r = 0.85). SSI was measured during ECMO flows of 20 to 100 ml/kg/min in both normal and dilated, poorly contracting hearts produced by 30 minutes of warm ischemia. After warm ischemia, end-systolic elastance, an index of contractility, decreased from 8.3 +/- 0.6 mm Hg/ml to 2.9 +/- 0.4 mm Hg/ml (p = 0.001) and peak systolic pressure decreased from 47.4 +/- 0.7 mm Hg to 37.5 +/- 0.08 mm Hg (p = 0.01). In normal hearts, as ECMO flow increased, SSI decreased from 10.5 +/- 2.2 mm Hg.sec to 7.7 +/- 0.8 mm Hg.sec at 60 ml/kg/min (p = 0.001). However, in postischemic hearts, SSI progressively increased from 6.6 +/- 0.3 mm Hg.sec before ECMO to 12.4 +/- 1.8 mm Hg.sec at ECMO = 100 ml/kg/min. These studies indicate that the initial effect of ECMO on the poorly contracting, dilated heart increases LV wall stress and that the increase in stress is proportional to ECMO flow. The increase in stress is primarily due to an increase in afterload, which more than offsets decreases in systolic and diastolic volumes.     

Reliable eighteen-hour lung preservation at 4 degrees and 10 degrees C by pulmonary artery flush after high-dose prostaglandin E1 administration.

Pulmonary preservation is improved by hypothermia, but the optimal preservation temperature is not known. The effects of two different preservation temperatures, 4 degrees and 10 degrees C, on lung function were studied in a canine left lung allograft survival model allowing selective perfusion of either lung. After donor treatment with high-dose prostaglandin E1, (25 micrograms/kg), lungs were flushed with modified Euro-Collins solution (50 ml/kg) and stored in Euro-Collins solution for 18 hours at 4 degrees C in group I (n = 8) and 10 degrees C in group II (n = 6). Pulmonary gas exchange and hemodynamics were compared on the day of transplantation (day 0) and 3 days later (day 3). Rapid, high-flow, low-pressure flush was achieved uniformly in both groups (flush time: group I, 35.1 +/- 2.4 second; group II, 35.3 +/- 3.0 seconds; p = 0.96; flush pressure: group I, 9.8 +/- 0.7 mm Hg; group II, 10.1 +/- 1.1 mm Hg; p = 0.8). Transplanted lungs provided similar excellent oxygenation in both groups on day 0 (arterial oxygen tension, group I, 451 +/- 82 mm Hg; group II, 497 +/- 37 mm Hg; p = 0.61; inspired oxygen fraction = 1.0) and day 3 (arterial oxygen tension, group I, 551 +/- 57 mm Hg; group II, 587 +/- 19 mm Hg; p = 0.55), with a statistically significant improvement from day 0 to day 3 in both groups (group I, p = 0.034; group II, p = 0.038). There was no difference in arterial carbon dioxide tension, base excess, cardiac output, blood pressure or pulmonary artery pressure between the two groups. We conclude that a large bolus of prostaglandin E1 into the pulmonary artery produces a high-flow, low-pressure flush with modified Euro-Collins solution; with this technique, equivalent, reliable 18-hour lung preservation can be achieved at 4 degrees and 10 degrees C flush and storage temperatures.     

Raffinose improves the function of rat pulmonary grafts stored for twenty-four hours in low-potassium dextran solution

OBJECTIVES: The perfect strategy for pulmonary graft preservation remains elusive. Experimental work supports the use of perfusates, such as Euro-Collins, University of Wisconsin, and low-potassium dextran solutions. We use low-potassium dextran solution in our clinical program, but we aim for continued improvement. The trisaccharide raffinose has been shown to be responsible for the efficacy of University of Wisconsin perfusate in lung preservation. Raffinose is superior to a variety of other saccharides for this purpose. We tested the hypothesis that the addition of raffinose to low-potassium dextran solution might further improve graft function. METHODS: In a randomized blinded study with a rat left lung transplant model, donor lungs were flushed with either standard low-potassium dextran solution or low-potassium dextran solution modified by the addition of 30 mmol/L raffinose (n = 5 for each group). Alprostadil (prostaglandin E(1), 500 microg/L) was added to the perfusates in accordance with our clinical practice. Grafts were stored inflated at 4 degrees C for 24 hours. After transplantation, recipients were ventilated with a fraction of inspired oxygen of 1 and a positive end-expiratory pressure of 2 cm H(2)O. Graft function was evaluated by measuring oxygenation at 2 hours after graft reperfusion, peak airway pressure throughout the reperfusion period, and the wet/dry lung weight ratio. RESULTS: The group receiving low-potassium dextran solution with raffinose demonstrated significantly higher oxygenation (oxygen tension, 370 +/- 45 mm Hg vs 150 +/- 64 mm Hg; P =.0025), lower peak airway pressures at 2 hours after lung reperfusion (11 +/- 2.7 mm Hg vs 16 +/- 2.4 mm Hg; P <.001), and a lower wet/dry weight ratio (4.7 +/- 1.26 vs 11 +/- 5. 0; P =.017). CONCLUSION: Modification of low-potassium dextran solution with the trisaccharide raffinose resulted in a significant improvement in graft function in this model and merits further evaluation with respect to the mechanisms involved.     

Intrathecal lidocaine prevents cardiovascular collapse and neurogenic pulmonary edema in a rat model of acute intracranial hypertension

Sympathetic hyperactivity during sudden intracranial hypertension leads to cardiovascular instability, myocardial dysfunction, and neurogenic pulmonary edema. Because spinal anesthesia is associated with sympatholysis, we investigated the protective effects of intrathecal lidocaine in a rodent model. Halothane-anesthetized rats were given a 10-microL intrathecal injection of saline (n = 10) or lidocaine 1% (n = 6). A subdural balloon catheter was inflated for 60 s to produce intracranial hypertension. Hemodynamics were monitored, and hearts and lungs were harvested for histological examination. In Saline versus Lidocaine-Treated rats, peak mean arterial blood pressure during balloon inflation was 115 +/- 4 mm Hg versus 78 +/- 8 mm Hg (P < 0.05), mean arterial blood pressure 30 min after balloon deflation was 47 +/- 2 mm Hg versus 67 +/- 3 mm Hg (P < 0.05), and lung weight was 1.54 +/- 0.03 g versus 1.41 +/- 0.04 g (P < 0.05), respectively. Cardiac dysrhythmias and electrocardiographic changes were more frequent in the Saline-Treated group (P < 0.05). Saline-Treated rats had extensive, hemorrhagic pulmonary edema, whereas the Lidocaine-Treated rats had only patchy areas of lung abnormality. Histological changes in the myocardium were rare, and no difference was found between the two groups. We conclude that intrathecal lidocaine prevents cardiovascular collapse and neurogenic pulmonary edema in a rat model of acute intracranial hypertension. IMPLICATIONS:In a rat model of intracranial balloon inflation, intrathecal lidocaine prevented cardiovascular collapse and neurogenic pulmonary edema. Descending neural pathways are involved in the development of cardiopulmonary complications associated with acute intracranial hypertension.     

Supplemental oxygen and carbon dioxide each increase subcutaneous and intestinal intramural oxygenation

Oxidative killing by neutrophils, a primary defense against surgical pathogens, is directly related to tissue oxygenation. We tested the hypothesis that supplemental inspired oxygen or mild hypercapnia (end-tidal PCO2 of 50 mm Hg) improves intestinal oxygenation. Pigs (25 +/- 2.5 kg) were used in 2 studies in random order: 1) Oxygen Study: 30% versus 100% inspired oxygen concentration at an end-tidal PCO2 of 40 mm Hg, and 2) Carbon Dioxide Study: end-tidal PCO2 of 30 mm Hg versus 50 mm Hg with 30% oxygen. Within each study, treatment order was randomized. Treatments were maintained for 1.5 h; measurements were averaged over the final hour. A tonometer inserted in the subcutaneous tissue of the left upper foreleg measured subcutaneous oxygen tension. Tonometers inserted into the intestinal wall measured intestinal intramural oxygen tension from the small and large intestines. Oxygen 100% administration doubled subcutaneous oxygen partial pressure (PO2) (57 +/- 10 to 107 +/- 48 mm Hg, P = 0.006) and large intestine intramural PO2 (53 +/- 14 to 118 +/- 72 mm Hg, P = 0.014); intramural PO2 increased 40% in the small intestine (37 +/- 10 to 52 +/- 25 mm Hg, P = 0.004). An end-tidal PCO2 of 50 mm Hg increased large intestinal PO2 approximately 16% (49 +/- 10 to 57 +/- 12 mm Hg, P = 0.039), whereas intramural PO2 increased by 45% in the small intestine (31 +/- 12 to 44 +/- 16 mm Hg, P = 0.002). Supplemental oxygen and mild hypercapnia each increased subcutaneous and intramural tissue PO2, with supplemental oxygen being most effective.     

Local myocardial overexpression of growth hormone attenuates postinfarction remodeling and preserves cardiac function

BACKGROUND: Ventricular remodeling with chamber dilation and wall thinning is seen in postinfarction heart failure. Growth hormone induces myocardial hypertrophy when oversecreted. We hypothesized that localized myocardial hypertrophy induced by gene transfer of growth hormone could inhibit remodeling and preserve cardiac function after myocardial infarction. METHODS: Rats underwent direct intramyocardial injection of adenovirus encoding either human growth hormone (n = 9) or empty null vector as control (n = 9) 3 weeks after ligation of the left anterior descending coronary artery. Analysis of the following was performed 3 weeks after delivery: hemodynamics, ventricular geometry, cardiomyocyte fiber size, and serum growth hormone levels. RESULTS: The growth hormone group had significantly better systolic cardiac function as measured by maximum left ventricular pressure (73.6 +/- 6.9 mm Hg versus control 63.7 +/- 7.8 mm Hg, p < 0.05) and maximum dP/dt (2845 +/- 453 mm Hg/s versus 1949 +/- 605 mm Hg/s, p < 0.005), and diastolic function as measured by minimum dP/dt (-2520 +/- 402 mm Hg/s versus -1500 +/- 774 mm Hg/s, p < 0.01). Ventricular geometry was preserved in the growth hormone group (ventricular diameter 12.2 +/- 0.7 mm versus control 13.1 +/- 0.4 mm, p < 0.05; borderzone wall thickness 2.0 +/- 0.2 mm versus 1.5 +/- 0.1 mm, p < 0.001), and was associated with cardiomyocyte hypertrophy (6.09 +/- 0.63 microm versus 4.66 +/- 0.55 microm, p < 0.005). Local myocardial expression of growth hormone was confirmed, whereas serum levels were undetectable after 3 weeks. CONCLUSIONS: Local myocardial overexpression of growth hormone after myocardial infarction resulted in cardiomyocyte hypertrophy, attenuated ventricular remodeling, and improved systolic and diastolic cardiac function. The induction of localized myocardial hypertrophy presents a novel therapeutic approach for the treatment of ischemic heart failure.     

Human aortocoronary grafts and nitric oxide release: relationship to pulsatile pressure

BACKGROUND: Short and long-term failure of saphenous vein grafts continues to be a significant problem for cardiac surgeons. The purpose of this study was to elucidate the early adaptive changes of human artery and vein conduits with respect to nitric oxide (NO) production under various pressure and pulsatile distention conditions. METHODS: Real-time amperometric NO determinations were made in an in vitro model using human saphenous vein segments (n = 12) and internal thoracic artery segments (n = 8) between 70 and 170 mm Hg, under static conditions recorded with a pressure transducer. Exposing the tissue to morphine (10(-6) M) also stimulated NO release. Under conditions in which the conduits were exposed to the respective pressures for 1 hour, they were then examined for their granulocyte-adhering potential using computer-assisted imaging techniques. RESULTS: A pressure-dependent decrease of NO release was found after 32 minutes of pulsatile pressure (170 mm Hg) in artery and vein, the latter of which appeared to be affected more negatively (p < 0.05; because many more observation points differed significantly after 32 minutes compared to 110 mm Hg values). In vessels maintained for 1 hour at these different pressures and then exposed to morphine (1 microM), stimulated NO release significantly diminished in the veins (artery 37.4 nM NO versus vein 18.1 nM NO; p < 0.05). Increased pressures also correlated with an increase in granulocyte adhesion to veins that could not be reduced following morphine exposure. CONCLUSIONS: Increased pressure and cyclic distention lead to loss of NO release and increased immunocyte adhesion, which are significantly more pronounced in saphenous vein than in internal thoracic artery, suggesting that in the long term this may contribute to the failure of saphenous vein conduits in coronary revascularization.     

Preserved gastric tonometric variables in cardiac surgical patients administered intravenous perflubron emulsion

Low gastric intramucosal pH (pHi) and an increased gastric-arterial PCO2 difference (CO2 gap) are markers of tissue hypoperfusion. Perfluorocarbons (PFCs) have a large oxygen-carrying capacity and release oxygen when encountering low tissue oxygen tension. Nine cardiac surgical patients instrumented for gastric tonometry were enrolled as part of a multicenter, randomized, single-blinded study of a PFC emulsion (perflubron emulsion [Oxygent]). Patients were randomized to receive PFC (n = 4) or placebo (n = 5) after intraoperative autologous blood harvesting by acute normovolemic hemodilution. At baseline there were no intergroup differences in tonometric-, hemodynamic-, or oxygen delivery-derived variables, e.g., Control group (pHi, 7.37 +/- 0.06; CO2 gap, 6.4 +/- 1.3 mm Hg) versus PFC group (pHi, 7.38 +/- 0.06; CO2 gap, 6.7 +/- 1.5 mm Hg). After acute normovolemic hemodilution, pHi was significantly lower (P < 0.01) in the Control group (7.22 +/- 0.25) than in the PFC group (7.44 +/- 0.25), and CO2 gap was significantly higher (P < 0.001) in the Control group (23.4 +/- 5.1 mm Hg) than in the PFC group (1.8 +/- 0.8 mm Hg). These differences in tonometric variables persisted during surgery. The PFC group showed a significantly (P < 0.007) shorter time to first bowel movement postoperatively (2.0 +/- 0.8 vs 5.4 +/- 1.6 days). Time to consumption of solid food was also shorter in the PFC group and almost achieved statistical significance (P = 0.056). IMPLICATIONS: This study suggests that the administration of perflubron emulsion prevents gastrointestinal tract ischemia in cardiac surgical patients and may preserve postoperative gastrointestinal tract function.