Minutes Of Normothermic Ischemia Research Articles

Effects of Ventilation on Lung Function after Normothermic Ischemia

The effects of atelectasis and hyperinflation were compared on immediate postischemic lung function and architecture, following normothermic ischemia. Thirty Sprague-Dawley rats were divided into 3 groups; 2 groups were subjected to 60 minutes of normothermic ischemia. The lungs were atelectatic in 10 (group A), they were hyperinflated to a pressure of 10 cm H2O in 10 (group B), and 10 rats served as nonischemic controls (group C). After 5 minutes of reperfusion, left pneumonectomies were performed and the lungs were examined histopathologically. There were no statistically significant differences in pulmonary venous blood oxygen tension or pH in the 3 groups. There was a significant difference between the compliance data of groups A and B (p < 0.05) and a highly significant difference between the compliance data of groups A and C (p < 0.001). Alveolar edema, perivascular edema, peribronchiolar edema, vascular congestion, and intrapulmonary hemorrhage were more frequent and more severe in the atelectatic group than in the hyperinflated group. The results indicate that postischemic injury occurred at an early stage in atelectatic lungs before any change in blood gas values and that superior postischemic preservation was achieved in lungs maintained in a hyperinflated state.

Behavioral testing does not exacerbate ischemic CA1 damage in gerbils.

Previous research studying ablative lesions has suggested that functional use may exacerbate brain injury. If true, this would have considerable ramifications not only for the mechanistic understanding of neuronal injury but also for the clinical use of physiotherapy. In this report the hypothesis that behavioral use of brain tissue exacerbates ischemic hippocampal injury was tested. Gerbils were subjected to sham operation or 5 minutes of normothermic ischemia. To produce borderline hippocampal CA1 injury and enhance susceptibility to exacerbation, 2 of 3 ischemic groups were cooled (>48 hours) beginning at 6 hours after ischemia. Increased use of the hippocampus was produced by a battery of tests involving 3 novel small mazes, a T maze, and an open field. One hypothermic group was not tested and served as a control. Behavioral testing failed to worsen ischemic damage since neuronal loss in the behaviorally tested and untested hypothermic groups was 12% and 8%, respectively, while that in the untreated ischemic group was 81% at a 1-month survival. Accordingly, protected CA1 cells tolerated the neuronal activity associated with behavioral testing. Concomitant with marked CA1 neuroprotection, a significant reduction in behavioral deficits with the hypothermic treatment was observed. Importantly, behavioral testing was found to transiently elevate brain temperature. CA1 neuronal survival was unaffected by behavioral testing or the associated mild fever. Hypothermia delayed for 6 hours provided sustainable CA1 neuroprotection.

Effect of intermittent warm blood cardioplegia on functional recovery after prolonged cardiac arrest

There is some evidence that continuous warm blood cardioplegia offers good myocardial protection; however, the effects of interrupting cardioplegia remain controversial. To study this, we compared the effects of continuous and intermittent antegrade warm (37 degrees C) blood cardioplegia on functional recovery after prolonged cardiac arrest (180 minutes). Twenty-four juvenile pigs were randomly assigned into four groups. Group 1 received continuous cardioplegia, group 2 underwent several periods of 15 minutes of cardioplegia interrupted by 5 minutes of normothermic ischemia, and group 3 underwent several periods of 10 minutes of cardioplegia interrupted by episodes of 10 minutes. The hearts of group 4 received no cardioplegia. Left ventricular systolic function was assessed from fractional left ventricular shortening and percentage left ventricular wall thickening, and left ventricular diastolic function was determined from the time constant of relaxation and the constant of myocardial stiffness. Systolic and diastolic functions were slightly depressed 1 and 2 hours after cross-clamp removal in all four groups, without significant differences among the groups. These data suggest that antegrade warm blood cardioplegia can be interrupted for up to 10 minutes without obvious negative effects on left ventricular function in the normal myocardium, provided that the intermittent doses of cardioplegia are sufficient to restore the metabolic demands of the arrested myocardium.

Ischemic preconditioning improves preservation with crystalloid cardioplegia

Ischemic preconditioning has not been investigated in a clinically relevant model of hypothermic multidose cardioplegia arrest. Using isolated rabbit hearts perfused on a Langendorff apparatus, ischemic preconditioning was investigated as an adjunct to crystalloid cardioplegia during a 2.5-hour ischemic period at 15 °C. After baseline functional data were obtained, ischemic preconditioning was induced with either 1 minute or 5 minutes of normothermic ischemia, followed by 5 minutes of reperfusion before the arrest period. Control hearts underwent no ischemic preconditioning. The control hearts exhibited a decrement in both the peak developed pressure and diastolic function, as measured by the slope of the diastolic pressure-volume relationship, of from 107 ± 2 to 68 ± 7 mm Hg ( p < 0.005) and from 0.99 ± 0.2 to 2.95 ± 0.44 mm Hg/0.1 mL ( p < 0.005), respectively. Hearts exposed to either 1 or 5 minutes of normothermic ischemia showed no significant change in the slope of the diastolic pressure-volume relationship. Hearts exposed to 1 or 5 minutes of normothermic ischemia also had a significant decrease in the peak developed pressure of from 107 ± 6 to 92 ± 2 mm Hg and from 102 ± 3 to 85 ± 4 mm Hg, respectively ( p < 0.05). However, ischemic preconditioning brought about a significant improvement in the postischemic peak developed pressure, as opposed to that seen for the control hearts ( p < 0.05). Creatine kinase washout was significantly higher in the control hearts only. High-energy phosphate levels, lactate levels, the percentage wet weight, and tissue creatine phosphate levels were not significantly different among the groups. Our findings suggest ischemic preconditioning may be useful in cases with an anticipated prolonged cross-clamp period, if this effect is validated by future investigations.

Nitric oxide-mediated, endothelium-dependent vasodilation is selectively attenuated in the postischemic extremity.

Attenuation of endothelium-dependent relaxing factor (EDRF) release may contribute to adverse sequelae commonly seen after reperfusion of an acutely ischemic extremity. The purpose of this study was to identify the compound responsible for the EDRF activity in the extremity and to evaluate its modulation by ischemia and reperfusion. Isolated rat hindlimbs were perfused at constant pressure with an albumin-enriched crystalloid buffer. Increasing log dose infusions of acetylcholine and nitroprusside were used to measure endothelium-dependent (EDRF-mediated) and endothelium-independent vasoreactivity, respectively. Graded reductions in total vascular resistance were seen in response to both agonists in the control group (n = 11). In the postischemic group (n = 7), 60 minutes of normothermic ischemia and 10 minutes of reperfusion reduced endothelium-dependent vasodilation to acetylcholine by approximately 40% (p < 0.01). Endothelium-independent vasodilation to nitroprusside was unaffected. NG-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of nitric oxide release, attenuated vasodilation to acetylcholine (p < 0.01) but not nitroprusside in both control and postischemic groups. Endothelium-dependent vasodilation in the rat hindlimb, mediated by nitric oxide, was selectively impaired by injury from ischemia and reperfusion. Strategies designed to minimize postischemic attenuation of nitric oxide release may be beneficial in the management of acute limb ischemia.

Response of the hypertrophied left ventricle to global ischemia

The hypertrophied left ventricle is at considerably greater risk for injury when subjected to global ischemia than is an otherwise normal heart. We evaluated the efficacy of verapamil, a calcium-channel blocking agent, as an adjunct to standard crystalloid cardioplegic solution in animals with left ventricular hypertrophy subjected to myocardial ischemia during cardiopulmonary bypass. Infracoronary aortic stenosis was produced in 15 mongrel puppies by plication of the noncoronary cusp of the aortic valve. Studies were conducted 3 to 4 months later. Left ventricular catheter-tip pressure transducers and major and minor axis ultrasonic dimension crystals were inserted, and the animals were then supported by cardiopulmonary bypass with 30 minutes of normothermic ischemia. Animals were randomized to receive either standard hyperkalemic crystalloid cardioplegic solution (n = 8) or the same solution with verapamil, 0.1 mg/kg (n = 7). After the 30 minutes of ischemia, the animals were supported on cardiopulmonary bypass for an additional 30 minutes and then separated from bypass. They were then studied for another 2 hours by measurement of myocardial adenosine triphosphate content, myocardial blood flow, systolic function with use of the end-systolic pressure/volume ratio, and compliance with use of the natural strain coefficient of the minor axis at 15 mm Hg end-diastolic pressure. There was a better recovery of systolic function in the animals treated with verapamil (89.2% versus 63.3%). The compliance as measured with use of the minor axis natural strain coefficient returned essentially to baseline in the group of animals treated with verapamil (0.236 +/- 0.038 before ischemia and 0.254 +/- 0.043 2 hours after ischemia), but it fell markedly in the control animals (0.219 +/- 0.027 before ischemia and 0.153 +/- 0.016 2 hours after ischemia). Myocardial adenosine triphosphate levels were not significantly different at any time during the study. Likewise, myocardial blood flow was not significantly different between groups. We conclude that the addition of verapamil to hyperkalemic cardioplegic solution improves recovery of both systolic and diastolic function after global ischemia in dogs with left ventricular hypertrophy resulting from aortic stenosis. The precise mechanism for this is unknown.