Normoxic ventilation after cardiac arrest reduces oxidation of brain lipids and improves neurological outcome

BACKGROUND AND PURPOSE: Increasing evidence that oxidative stress contributes to delayed neuronal death after global cerebral ischemia has led to reconsideration of the prolonged use of 100% ventilatory O2 following resuscitation from cardiac arrest. This study determined the temporal course of oxidation of brain fatty acyl groups in a clinically relevant canine model of cardiac arrest and resuscitation and tested the hypothesis that postischemic ventilation with 21% inspired O2, rather than 100% O2, results in reduced levels of oxidized brain lipids and decreased neurological impairment. METHODS: Neurological deficit scoring and high performance liquid chromatography measurement of fatty acyl lipid oxidation were used in an established canine model using 10 minutes of cardiac arrest followed by resuscitation with different ventilatory oxygenation protocols and restoration of spontaneous circulation for 30 minutes to 24 hours. RESULTS: Significant increases in frontal cortex lipid oxidation occurred after 10 minutes of cardiac arrest alone with no reperfusion and after reperfusion for 30 minutes, 2 hours, and 24 hours (relative total 235-nm absorbing peak areas=7.1+/-0.7 SE, 17.3+/-2.7, 14.2+/-3.2, 16.1+/-1.0, and 14.0+/-0.8, respectively; n=4, P<0.05). The predominant oxidized lipids were identified by gas chromatography/mass spectrometry as 13- and 9-hydroxyoctadecadienoic acids (13- and 9-HODE). Animals ventilated on 21% to 30% O2 versus 100% O2 for the first hour after resuscitation exhibited significantly lower levels of total and specific oxidized lipids in the frontal cortex (1.7+/-0.1 versus 3.12+/-0.78 microg 13-HODE/g wet wt cortex., n=4 to 6, P<0.05) and lower neurological deficit scores (45.1+/-3.6 versus 58.3+/-3.8, n=9, P<0.05). CONCLUSIONS: With a clinically relevant canine model of 10 minutes of cardiac arrest, resuscitation with 21% versus 100% inspired O2 resulted in lower levels of oxidized brain lipids and improved neurological outcome measured after 24 hours of reperfusion. This study casts further doubt on the appropriateness of present guidelines that recommend the indiscriminate use of 100% ventilatory O2 for undefined periods during and after resuscitation from cardiac arrest.     

Serum neuron-specific enolase as early predictor of outcome after cardiac arrest

OBJECTIVE: To examine the prognostic value of serum neuron-specific enolase for early prediction of outcome in patients at risk for anoxic encephalopathy after cardiac arrest. DESIGN: Prospective study. SETTING: Coronary intensive care unit of the University of Heidelberg. PATIENTS: Forty-three patients (66.8 +/- 12.7 [SD] yrs, range 33 to 85) who had had either primary or secondary cardiac arrest, followed by cardiopulmonary resuscitation (CPR). INTERVENTIONS: Serial blood samples and clinical examinations. MEASUREMENTS AND MAIN RESULTS: Serum neuron-specific enolase concentrations were determined after CPR on 7 consecutive days. Twenty-five patients remained comatose and subsequently died; 18 patients survived the first 3 months and had no relevant functional deficit at 3-month follow-up. Neuron-specific enolase concentrations were correlated with neurologic outcome. Concentrations of >33 ng/mL predicted persistent coma with a high specificity (100%) and a positive predictive value of 100%. Overall sensitivity was 80%, with a negative predictive value of 78%. Serum concentrations of neuron-specific enolase exceeded this cutoff value no more than 3 days after cardiac arrest in 95% of patients in whom these concentrations had exceeded 33 ng/mL. CONCLUSIONS: In patients who have been resuscitated after cardiac arrest, serum neuron-specific enolase concentrations of >33 ng/mL predict persistent coma with a high specificity. Values below this cutoff level do not necessarily indicate complete recovery, because this method has a sensitivity of 80%.     

Biofeedback improves functional outcome after sphincteroplasty

Pax genes are expressed in specific patterns in the nervous system during development and in the adult. Recent findings suggest a link between the expression of Pax-2 and axonal guidance. Mice with a targeted deletion of Pax-2 are an excellent tool for studying axonal pathfinding at the molecular level, especially with respect to the optic chiasm. The date reviewed here suggest that Pax-2 regulates the expression of surface molecules involved in contact attraction and that the mutual regulation of the expression of Pax-2 and the Sonic hedgehog gene is of importance in the formation of the chiasm region.     

Myocardial dysfunction after successful resuscitation from cardiac arrest

OBJECTIVE: To investigate the functional and metabolic changes in the myocardium after successful resuscitation from cardiac arrest. DESIGN: Prospective, randomized, sham-controlled study. SETTING: Animal laboratory at a university center. SUBJECTS: Domestic pigs. INTERVENTIONS: Electric induction of ventricular fibrillation by alternating current delivered to the right ventricular endocardium through a pacing electrode. Electric defibrillation was attempted after an interval of 12 mins of ventricular fibrillation, which included 4 mins of untreated ventricular fibrillation and 8 mins of precordial compression in 13 animals, seven of which were successfully resuscitated. Seven additional animals were randomized to serve as "sham" controls, in which cardiac arrest was not induced. MEASUREMENTS AND MAIN RESULTS: Left ventricular pressure-volume relationships utilizing the conductance method were obtained in conjunction with conventional hemodynamic and metabolic measurements at baseline and during a 6-hr interval after successful cardiac resuscitation. Progressive and striking increases in left ventricular volumes were observed after successful cardiac resuscitation. The end-diastolic volume increased from a prearrest level of 89 +/- 21 mL to a maximum of 154 +/- 53 mL (p<.05) at 360 mins after successful resuscitation. The time-coincident end-systolic volume increased from 54 +/- 21 to 126 +/- 54 mL (p<.05), such that the ejection fraction was reduced from 0.41 +/- 0.10 to 0.20 +/- 0.07 ( p<.05). Ventricular dilation was associated with marked reductions in stroke volume and ventricular work. However, compensatory increases in heart rate maintained cardiac output at levels that sustained adequate systemic oxygen delivery. The slope of the end-systolic pressure-volume relationships progressively decreased from 5.04 +/- 1.88 to 2.00 +/- 0.57 mm Hg/mL (p<.05) at 360 mins after successful resuscitation. The volume intercept at left ventricular pressure of 100 mm Hg increased from 43 +/- 19 to 94 +/- 51 mL (p=.03). Both the decrease in the slope and the increase in the volume intercept were characteristic of progressive impairment in contractile function. The rate of left ventricular pressure decrease was unchanged. Accordingly, no substantial changes in lusitropic properties were identified. Despite large increases in end-diastolic volume, the end-diastolic pressure remained unchanged. CONCLUSION: Postresuscitation myocardial dysfunction in this animal model was characterized by impaired contractile function, decreased work capability, and ventricular dilation.     

Mild hypothermia after cardiac arrest in dogs does not affect postarrest cerebral oxygen uptake/delivery mismatching

PURPOSE: To compare measurements of cerebral arteriovenous oxygen content differences (oxygen extraction ratios, oxygen utilization coefficients) in dogs after cardiac arrest, resuscitated under normothermia vs. mild hypothermia for 1-2 h or 12 h. METHODS: In 20 dogs, we used our model of ventricular fibrillation (no blood flow) of 12.5 min, reperfusion with brief cardiopulmonary bypass, and controlled ventilation, normotension, normoxemia, and mild hypocapnia to 24 h. We compared a normothermic control Group I (37.5 degrees C) (n = 8); with brief mild hypothermia in Group II (core and tympanic membrane temperature about 34 degrees C during the first hour after arrest) (n = 6); and with prolonged mild hypothermia in Group III (34 degrees C during the first 12 h after arrest) (n = 6). RESULTS: In Group I, the cerebral arteriovenous O2 content difference was 5.6 +/- 1.6 ml/dl before arrest; was low during reperfusion (transient hyperemia) and increased (worsened) significantly to 8.8 +/- 2.8 ml/dl at 1 h, remained increased until 18 h, and returned to baseline levels at 24 h after reperfusion. These values were not significantly different in hypothermic Groups II and III. The cerebral venous (saggital sinus) PO2 (PssO2) was about 40 mmHg (range 29-53) in all three groups before arrest and decreased significantly below baseline values, between 1 h and 18 h after arrest; the lowest mean values were 19 +/- 19 mmHg in Group I, 15 +/- 8 in Group II (NS), and 21 +/- 3 in Group III (NS). Postarrest PssO2 values of < or = 20 mmHg were found in 6/8 dogs in Group I, 5/6 in Group II and 4/6 in Group III. Among the 120 values of PssO2 measured between 1 h and 18 h after arrest, 32 were below the critical value of 20 mmHg. CONCLUSIONS: After prolonged cardiac arrest, critically low cerebral venous O2 values suggest inadequate cerebral O2 delivery. Brief or prolonged mild hypothermia after arrest does not mitigate the postarrest cerebral O2 uptake/delivery mismatching.     

Lidocaine pharmacokinetics after cardiac arrest and external cardiopulmonary resuscitation

Although prolonged cardiopulmonary resuscitation may impair drug metabolism, plasma lidocaine concentrations tended to remain within the therapeutic range after cardiopulmonary resuscitation lasting up to 30 minutes. Thus, the effects of cardiopulmonary resuscitation on lidocaine metabolism appear to be of little importance in the usual clinical situation.     

Visceral, hematologic and bacteriologic changes and neurologic outcome after cardiac arrest in dogs. The visceral post-resuscitation syndrome

We studied the post-resuscitation syndrome in 42 healthy dogs after normothermic ventricular fibrillation cardiac arrest (no blood flow) of 7.5, 10, or 12.5 min duration, reversed by standard external cardiopulmonary resuscitation (CPR) (< or = 10 min) and followed by controlled ventilation to 20 h and intensive care to 72 h. We reported previously, in the same dogs, no difference in resuscitability, mortality, or neurologic outcome between the three insult groups. There was no pulmonary dysfunction, but post-arrest cardiovascular failure, of greater severity in the 12.5 min arrest group. This report concerns renal, hematologic, hepatic and bacteriologic changes. Renal function recovered within 1 h after arrest, without permanent dysfunction. Clotting derangements at 1-24 h postarrest reflect transient disseminated intravascular coagulation with hypocoagulability, more severe after longer arrests, which resolved by 24 h after arrest. Hepatic dysfunction was transient but more severe in the animals that did not recover consciousness and correlated with neurologic dysfunction, but not with brain histologic damage. Bacteremia was present in all animals postarrest. We conclude that in the previously healthy organism after cardiac arrest of 7.5-12.5 min no flow, visceral and hematologic changes, although transient, can retard neurologic recovery.     

Specific changes in human brain following reperfusion after cardiac arrest

BACKGROUND AND PURPOSE: Very few reports are available on serial changes in human brain after cardiac arrest. The primary objective of this study is to investigate sequential neuroradiological changes in patients remaining in a persistent vegetative state following resuscitation after cardiac arrest. METHODS: We repeatedly studied eight vegetative patients resuscitated from unexpected out-of-hospital cardiac arrest using computed tomographic (CT) scanning and high-field magnetic resonance (MR) imaging at 1.5 T. RESULTS: In seven of the eight patients, CT scans obtained between days 2 and 6 features symmetrical low-density lesions in the bilateral caudate, lenticular, and/or thalamic nuclei. These ischemic lesions were persistently of low density on serial CT scans. In these seven patients, MR images demonstrated what were thought to be hemoglobin degradation products derived from minor hemorrhages localized in the bilateral basal ganglia, thalami, and/or substantia nigra. Diffuse brain edema in the acute stage and diffuse brain atrophy in the chronic stage were consistent neuroradiological findings. No abnormal enhanced lesions were demonstrated by CT scans. CONCLUSIONS: The most characteristic findings on high-field MR images were symmetrical lesions in the bilateral basal ganglia, thalami, and/or substantia nigra with specific changes suggestive of minor hemorrhages that were not evident on CT scans. We speculate that these minor hemorrhages result from diapedesis of red blood cells in these regions during the reperfusion period through the endothelium disrupted by ischemia-reperfusion insult.     

pH strategies and cerebral energetics before and after circulatory arrest

The pH-stat strategy compared with the alpha-stat strategy provides more rapid recovery of brain high-energy phosphate stores and intracellular pH after 1 hour of hypothermic circulatory arrest in pigs. Possible mechanisms for this difference are (1) improved oxygen delivery and homogeneity of brain cooling before deep hypothermic circulatory arrest and (2) greater cerebral blood flow and reduced reperfusion injury owing to extracellular acidosis during the rewarming phase. To identify which of these mechanisms is predominant, we studied 49 4-week-old piglets undergoing 1 hour of deep hypothermic circulatory arrest. Four groups were defined according to cooling/rewarming strategy: alpha/alpha, alpha/pH, pH/alpha, and pH/pH. In 24 animals cerebral high-energy phosphate levels and intracellular pH were measured by magnetic resonance spectroscopy (alpha/alpha group 7, alpha/pH group 5, pH/alpha group 7, pH/pH group 5). In 25 animals cerebral blood flow was measured by labeled microspheres, cerebral metabolic rate by oxygen and glucose extraction, and the redox state of cytochrome aa3 and hemoglobin oxygenation by near infrared spectroscopy (alpha/alpha group 7, alpha/pH group 5, pH/alpha group 7, pH/pH group 6). Cerebral blood flow was greater with pH-stat than alpha-stat during cooling (56.3% +/- 3.7% versus 32.9% +/- 2.1% of normothermic baseline values, p < 0.001). Cytochrome aa3 values became more reduced during cooling with alpha-stat than with pH-stat (p = 0.049). Recovery of adenosine triphosphate levels in the initial 45 minutes of reperfusion was more rapid in group pH/pH compared with that in the other groups (p = 0.029). Recovery of cerebral intracellular pH in the initial 30 minutes was faster in group pH/pH compared with that in group alpha/alpha (p = 0.026). Intracellular pH became more acidic during early reperfusion only in group alpha/alpha, whereas it showed continuous recovery in the other groups. This study suggests that there are mechanisms in effect during both the cooling and rewarming phases before and after deep hypothermic circulatory arrest that could contribute to an improved cerebral outcome with pH-stat relative to more alkaline strategies.     

Patient-controlled analgesia versus patient-controlled analgesia plus continuous infusion after hip replacement surgery

OBJECTIVE: To compare the efficacy and adverse effect profile of patient-controlled analgesia (PCA) versus PCA plus continuous infusion (PCACI) after hip replacement surgery. DESIGN: Prospective, randomized, open pilot study. SETTING: Large teaching institution. PARTICIPANTS: Thirty-four patients undergoing hip replacement or revision of hip replacement surgery. INTERVENTIONS: Patients were randomized to receive PCA morphine: 1 mg with 6-minute lockout, or PCACI, using the same dose, with a 0.5-1 mg/h continuous infusion. Pain intensity, sedation, narcotic use, injection/attempt ratio (I/A), and adverse effects were assessed. RESULTS: No significant differences in pain intensity were identified. Morphine use was not different between groups: PCA 61.8 +/- 35.0 and PCACI 74.2 +/- 54.9 mg (p =0.394). A trend toward an increased 12-hour I/A ratio was evident in the PCACI group: PCA 0.73 +/- 0.18 and PCACI 0.86 +/- 0.17 (p =0.073). Patient-reported adverse effects, sedation, and inability to sleep secondary to pain occurred similarly. Eight of 18 PCACI patients required discontinuation of either the continuous infusion mode or of PCA therapy entirely secondary to adverse effects. CONCLUSIONS: When compared with PCA therapy, PCACI was not associated with improved pain control and more patients receiving PCACI required discontinuation of therapy secondary to adverse effects.     

Portal and peripheral blood immunoreactive insulin concentrations after glucose infusion during gastrectomy

We evaluated portal and peripheral blood immunoreactive insulin concentrations (IRI) after glucose infusion in patients undergoing gastrectomy. Seventy-four patients were divided into following two groups: 68 received 25g glucose infusion in an hour (glucose group), and the remainder received no glucose (control group). Portal blood IRI level in glucose group was about thirty-fold higher than that in control group. However, peripheral blood IRI did not correlate with portal blood IRI in glucose group. In addition, significant negative correlation between portal blood IRI and blood glucose was observed in glucose group. Our results reveal that adequate pancreatic insulin secretion occurs after glucose infusion during gastrectomy, but peripheral blood IRI does not reflect this pancreatic insulin secretion. The results also suggest that blood glucose may be regulated by the liver under these conditions.     

Diaspirin cross-linked hemoglobin resuscitation improves cerebral perfusion after head injury and shock

BACKGROUND: Shock associated with traumatic brain injury (TBI) doubles the mortality of TBI alone by inducing a secondary ischemic injury. Rapid correction of cerebral perfusion pressure (CPP) is thought to be essential to improving outcome. Diaspirin cross-linked hemoglobin (DCLHb) has been shown to improve cerebral blood flow, increase mean arterial pressure (MAP), and reduce lesion size in models of occlusive cerebral ischemia but has not been evaluated in a model of TBI combined with hemorrhagic shock. METHODS: We studied the effects of DCLHb resuscitation in a porcine model of cryogenic TBI and hemorrhagic shock (MAP = 50 mmHg). After combined insults, animals were randomized to receive a bolus of 4 mliters/kg of either lactated Ringer's solution (n = 5) or DCLHb (n = 6). Lactated Ringer's solution was then infused in both groups to maintain MAP at baseline. Shed blood was returned 1 hour after the initiation of resuscitation (R1). Animals were studied for 24 hours. RESULTS: DCLHb infusion resulted in a significantly greater MAP at R1 and R24 (95 +/- 4 vs. 82 +/- 2 and 99 +/- 3 vs. 85 +/- 3 mm Hg, respectively) and a significantly greater CPP at R1 and R24 (83 +/- 10 vs. 68 +/- 5 and 89 +/- 6 vs. 71 +/- 11 mm Hg, respectively). Intracranial pressure was lower in the DCLHb group, but this difference was not significant. There was no significant difference between the groups in cerebral oxygen delivery. DCLHb animals required less fluid to maintain MAP (12,094 +/- 552 vs. 15,542 +/- 1094 mliters, p < 0.05). CONCLUSION: These data suggest that DCLHb is beneficial in the early resuscitation of head injury and shock and that further investigation is warranted. Key Words: Diaspirin cross-linked hemoglobin, Head injury, Shock, Cerebral perfusion pressure.     

Insulin levels after portal and systemic insulin infusion differ in a dose-dependent fashion

BACKGROUND: Before the advent of the falloposcope, the endosalpinx usually evaded endoscopic evaluation. The healthy condition of the tubal epithelium and the patency of the tube are important for development and transportation of early stage embryos. METHODS: Twenty patients had tubal occlusion diagnosed by hysterosalpingography, including 10 cases of hydrosalpinx, five cases of interstitial occlusion and five cases of fimbrial occlusion. Falloposcopy with a linear everting catheter and laparoscopy were performed simultaneously to evaluate tubal lumens and peritubal conditions. RESULTS: An attempt was made to cannulate 30 fallopian tubes in 20 cases with a falloposcope, using a nonhysteroscopic transvaginal approach through a linear everting catheter. The success rate was 93% (28/30). In 15 cases of hydrosalpinx or fimbrial obstruction, 10 patients (67%) were considered to be suitable for in vitro fertilization because of flattened mucosa in the endosalpinx and endotubal adhesions. Normal mucosa was noted in only four patients (27%), who were advised to have tuboplasty. One patient (6%) had normal mucosa without tubal occlusion. In two of the five cases of interstitial occlusion, dye (methylene blue) could not pass the interstitial portion of the fallopian tube when chromopertubation was performed twice. This tubal obstruction was overcome with the linear everting catheter. One patient had the complication of an ampulla wall perforation. CONCLUSIONS: In patients with fallopian tube disease, falloposcopy is a useful technique for evaluating the endosalpinx and providing information for selecting further treatment. In some cases of interstitial occlusion, it may also have a therapeutic effect.     

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

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Survival after cardiac arrest outside hospital over a 12-year period in Gothenburg

BACKGROUND: A two-tiered ambulance system with a mobile coronary care unit and standard ambulance has operated in Gothenburg (population 434,000) since 1980. Mass education in cardiopulmonary resuscitation (CPR) commenced in 1985 and in 1988 semiautomatic defibrillators were introduced. Aim: To describe early and late survival after cardiac arrest outside hospital over a 12-year period. Target population: All patients with prehospital cardiac arrest in Gothenburg reached by mobile coronary care unit or standard ambulance between 1980 and 1992. RESULTS: The number of patients with cardiac arrest remained fairly steady over time. Among patients with witnessed ventricular fibrillation, the time to defibrillation decreased over time. The proportion of patients in whom bystander initiated CPR was increased only moderately over time. The proportion of patients given medication such as lignocaine and adrenaline successively increased. The number of patients with cardiac arrest who were discharged from hospital per year remained steady between 1981 and 1990 (20 per year), but increased during 1991 and 1992 to 41 and 31 respectively. CONCLUSIONS: Improvements in the emergency medical service in Gothenburg over a 12-year period have lead to: (1) a shortened delay time between cardiac arrest and first defibrillation and (2) an improved survival of patients with cardiac arrest outside hospital probably explained by this shortened delay time.     

Depression of cardiac function after deep hypothermic circulatory arrest in deeply anesthetized neonatal lambs

Cardiac dysfunction is common after neonatal cardiac operations. Previous in vivo studies in neonatal animal models however, have failed to demonstrate decreased left ventricular function after ischemia and reperfusion. Cardiac dysfunction may have been masked in these studies by increased endogenous catecholamine levels associated with the use of light halothane anesthesia. Currently, neonatal cardiac operations are often performed with deep opiate anesthesia, which suppresses catecholamine surges and may affect functional recovery. We therefore examined the recovery of left ventricular function after ischemia and reperfusion in neonatal lambs anesthetized with high-dose fentanyl citrate (450 micrograms/kg administered intravenously). Seven intact neonatal lambs with open-chest preparation were instrumented with left atrial and left ventricular pressure transducers, left ventricular dimension crystals, and a flow transducer. The lambs were cooled (< 18 degrees C) on cardiopulmonary bypass (22 +/- 6 minutes), exposed to deep hypothermic circulatory arrest (46 +/- 1 minutes), and rewarmed on cardiopulmonary bypass (30 +/- 10 minutes). Catecholamine levels and indexes of left ventricular function were determined before (baseline) and 30, 60, 120, 180, and 240 minutes after termination of cardiopulmonary bypass. Levels of epinephrine, norepinephrine, and dopamine were unchanged from baseline values. Left ventricular contractility (slope of end-systolic pressure-volume relationship) was depressed from baseline value (31.7 +/- 9.3 mm Hg/ml) at 30 minutes (15.7 +/- 6.4 mm Hg/ml) and 240 minutes (22.7 +/- 6.4 mm Hg/ml) but unchanged between 60 and 180 minutes. Left ventricular relaxation (time constant of isovolumic relaxation) was prolonged from baseline value (19.0 +/- 3.0 msec) at 30 minutes (31.4 +/- 10.0 msec) and 240 minutes (22.1 +/- 2.8 msec) but unchanged between 60 and 180 minutes. Afterload (left ventricular end-systolic meridional wall stress) was decreased at 30, 60, and 240 minutes. Indexes of global cardiac function (cardiac output, stroke volume), preload (end-diastolic volume), and left ventricular compliance (elastic constant of end-diastolic pressure-volume relationship) were unchanged from baseline values. In deeply anesthetized neonatal lambs exposed to ischemia and reperfusion, left ventricular contractility, relaxation, and afterload are markedly but transiently depressed early after reperfusion and mildly depressed late after reperfusion.