Effects of Oxygen Concentrations on Postresuscitation Myocardial Oxidative Stress and Myocardial Function in a Rat Model of Cardiopulmonary Resuscitation.

OBJECTIVE: Lipid peroxidation induced by free-radical species plays a prominent role in myocardial injury following ischemia and reperfusion. However, there is a lack of data in different oxygen concentrations on myocardial lipid peroxidation during the early phase of reperfusion. In this study, we investigated whether ventilation with medium or normal concentration of oxygen would decrease the severity of myocardial lipid peroxidation and postresuscitation myocardial dysfunction. DESIGN: Prospective, randomized, controlled experimental study. SETTING: University-affiliated animal research institution. SUBJECTS: Sixty-three healthy male Sprague-Dawley rats. INTERVENTIONS: Animals were randomized into three groups: 1) 100% group, 2) 50% group, and 3) 21% group. Ventricular fibrillation was induced and untreated for 8 minutes, and defibrillation was attempted after 8 minutes of cardiopulmonary resuscitation. Ventilation with 100%, 50%, or 21% oxygen was initiated in all groups during cardiopulmonary resuscitation and 1 hour following the return of spontaneous circulation. Normoxic ventilation was maintained thereafter. MEASUREMENTS AND MAIN RESULTS: Myocardial function, including ejection fraction and myocardial performance index, were measured at baseline, 4, or 72 hours after resuscitation. Blood samples were drawn at baseline, 15 minutes, 1, 4, or 72 hours after resuscitation for the measurements of blood gas or biomarkers. Significantly better myocardial function and longer duration of survival were observed in the 50% group. Compared with the 21% and 100% groups, a mild hyperoxia and greater oxygen extraction with lower 8-iso-prostaglandin F2α were observed in the 50% group. Pearson correlation analysis confirmed that 8-iso-prostaglandin F2α was positively correlated with myocardial performance index at 4 hours postresuscitation. CONCLUSIONS: In a rat model of cardiac arrest and resuscitation, ventilation with 50% inspired oxygen during early postischemic reperfusion phase contributed to a decreased lipid peroxidation and a better myocardial function and duration of survival.

CHANGES IN SUBLINGUAL MICROCIRCULATION IS CLOSELY RELATED WITH THAT OF BULBAR CONJUNCTIVAL MICROCIRCULATION IN A RAT MODEL OF CARDIAC ARREST.

Following successful resuscitation, a significantly impaired microcirculation has been identified. The severity of the impairment of microcirculation is closely related to that of vital organ dysfunction. Sublingual microcirculation is a traditional site for the measurement of tissue perfusion. In the present study, we investigated the bulbar conjunctival microcirculatory alterations following CPR and its relationship with the changes of sublingual microcirculation in a rat model of cardiac arrest.Male Sprague-Dawley rats (450-550 g) were utilized. Ventricular fibrillation was induced and untreated for 8 min followed by 8 min of CPR. Sublingual and bulbar conjunctival microcirculatory blood flow was visualized by a sidestream dark-field imaging device at baseline, 30 min, 1, 2, 4, and 8 h post-resuscitation. Both perfused vessel density (PVD) and microcirculatory flow index (MFI) were recorded.The post-resuscitation PVD and MFI were significantly decreased in both sublingual and bulbar conjunctival sites. Sublingual PVD decreased from baseline of 5.9 ± 0.3 to 3.1 ± 0.4 n/mm at 30 min post-resuscitation and MFI from 3.0 ± 0.0 to 1.5 ± 0.3 (both P < 0.05 vs. baseline). Bulbar conjunctival PVD was significantly reduced from baseline of 6.5 ± 0.6 to 3.9 ± 0.5 n/mm at 30 min post-resuscitation and MFI from 3.0 ± 0.0 to 1.2 ± 0.4 (both P < 0.05 vs. baseline). PVD, MFI, and cardiac function did not change significantly from the 30-min measurements in the surviving rats throughout the remainder of the study (both P > 0.05 vs. 30-min post-resuscitation). The decreases in sublingual microcirculatory blood flow were closely correlated with the reductions of bulbar conjunctival microcirculatory blood flow (PVD: r = 0.87, P < 0.05; MFI: r = 0.92, P < 0.05). Myocardial function was significantly impaired in all animals after resuscitation when compared with baseline values (P < 0.05). The impairments of both sublingual and bulbar conjunctival microcirculation were significantly correlated with the impairment of myocardial function.In the rat model of cardiac arrest, the changes in sublingual microcirculatory blood flow are closely correlated with that of bulbar conjunctival microcirculatory blood flow after successful resuscitation. The changes are correlated with the severity of post-resuscitation myocardial dysfunction. Our study testified sublingual site could be substituted by bulbar conjunctival at least in the rat model of cardiac arrest. The measurement of conjunctival microcirculation may provide an accessible and convenient option as sublingual site for monitoring microcirculation in humans.

Mild hypothermia preserves cerebral cortex microcirculation after resuscitation in a rat model of cardiac arrest.

OBJECTIVE: Mild hypothermia improves the outcomes of comatose patients after cardiac arrest. Its neuroprotective mechanism is not fully understood. We investigated the effects of mild hypothermia on cerebral cortex microcirculation and cerebral oxygen extraction ratio. METHODS: Twenty-five rats were randomized into the hypothermic group (HT), normothermic group (NT) or the sham control group. Ventricular fibrillation was electrically induced and untreated for 8 min, followed by 8 min of precordial compressions and mechanical ventilations. The core temperature in the HT group was reduced to 33±0.5 °C at 14 min after ROSC with a combination of ice packs, an electrical fan and a cooling blanket. The temperature was maintained at 33 °C for 8h. Hemodynamics, arterial and jugular venous blood gases and cerebral cortex microcirculation were measured at baseline, 2, 4 and 8h after ROSC. RESULTS: Microvascular flow index was significantly reduced in the NT and HT groups when compared with the SC group. A significant lesser reduction in microvascular flow index was observed in the HT group when compared with the NT group. Mild hypothermia reduced the cerebral oxygen extraction ratio after resuscitation when compared with the NT group. CONCLUSION: Mild hypothermia improves the cerebral cortex microcirculatory blood supply/oxygen uptake mismatching after resuscitation. This may provide an additional cerebral protection.

The effects of α- and ß-adrenergic blocking agents on postresuscitation myocardial dysfunction and myocardial tissue injury in a rat model of cardiac arrest.

We investigated the relationship between the severity of postresuscitation (PR) myocardial tissue injury and myocardial dysfunction after the administration of epinephrine as well as the protective effects of α- and ß-adrenergic blocking agents. Forty male Sprague-Dawley rats were randomized into 6 groups: (1) placebo; (2) epinephrine; (3) epinephrine pretreated with α1-blocker (prazosin); (4) epinephrine pretreated with α2-blocker (yohimbine); (5) epinephrine pretreated with ß-blocker (propranolol); and (6) epinephrine pretreated with ß- plus α1-blocker (propranolol and prazosin). Cardiopulmonary resuscitation was initiated after 8 minutes of untreated ventricular fibrillation and continued for an additional 8 minutes. The myocardial function and the serum concentrations of troponin I (Tn I) and N-terminal probrain natriuretic peptide (NT-proBNP) were measured at baseline and after resuscitation. After resuscitation, both Tn I and NT-proBNP were significantly increased in all groups, especially in the epinephrine and epinephrine pretreated with α2-blocker groups. Significantly better PR myocardial function and neurologic deficit score were observed in epinephrine pretreated with the α1- or ß-blocker with decreased releases of Tn I and NT-proBNP. However, the most significant improvements were observed in the animals pretreated with ß- plus α1-blocker. The present study demonstrated that myocardial stunning may not be the only mechanism of PR myocardial dysfunction. Administration of epinephrine increased the severity of PR myocardial tissue injury and dysfunction. The ß- and ß- plus α1-blocker pretreatment significantly reduced the severity of PR myocardial tissue injury and myocardial dysfunction with better neurologic function and prolonged duration of survival.

Remote ischemic preconditioning mitigates myocardial and neurological dysfunction via K(ATP) channel activation in a rat model of hemorrhagic shock.

Severe hemorrhagic shock and resuscitation is a state of global body ischemia and reperfusion that causes myocardial and cerebral dysfunction. We investigated whether remote ischemic preconditioning (RIPC) would reduce myocardial and cerebral ischemia and reperfusion injuries after hemorrhagic shock as the result of the K(ATP) channel activation. Twenty-one male rats were randomized into three groups: RIPC, RIPC with K(ATP) channel blocker, and control. Remote ischemic preconditioning was induced by four cycles of 5 min of limb ischemia followed by reperfusion for 5 min. Hemorrhagic shock was induced by removing 50% of the estimated total blood volume during an interval of 1 h. Thirty minutes after the completion of bleeding, the animals were reinfused with shed blood during the ensuing 30 min. The animals were monitored for 2 h and observed for an additional 72 h. Myocardial function was measured by echocardiography, and sublingual microcirculation was measured by a sidestream dark-field imaging device at baseline, 1 h after bleeding, 30 min after the completion of bleeding, 30 min after reinfusion, and hourly intervals thereafter. The survival and neurological function were evaluated at 12, 24, 48, and 72 h after reinfusion. At 2 h after reinfusion, ejection fraction and myocardial performance index were significantly better in the RIPC group than in the control group (P < 0.01). The sublingual microvascular flow index and perfused vessel density were significantly greater after reinfusion in the RIPC group than that in the control group (P < 0.01). The duration of survival was significantly longer, and neurological deficit score was significantly better in the RIPC group than the control animals (P < 0.01). Pretreatment with the K(ATP) channel blocker (glibenclamide) completely abolished the myocardial and cerebral protective effects of RIPC. We demonstrate, for the first time, that after severe hemorrhagic shock and resuscitation, RIPC mitigated myocardial and neurological dysfunction with improved survival by activation of the K(ATP) channel.

Post-resuscitation intestinal microcirculation: its relationship with sublingual microcirculation and the severity of post-resuscitation syndrome.

OBJECTIVE: Post-resuscitation syndrome has been recognized as one of the major causes of the poor outcomes of cardiopulmonary resuscitation. The aims of this study were to investigate the intestinal microcirculatory changes following cardiopulmonary resuscitation and relate those changes to sublingual microcirculation and the severity of post-resuscitation syndrome as measured by myocardial function and serum inflammatory cytokine levels. METHODS: Twenty-five rats were randomized into three groups: (1) short duration of cardiac arrest (n=10): ventricular fibrillation (VF) was untreated for 4 min prior to 6 min of cardiopulmonary resuscitation (CPR); (2) long duration of cardiac arrest (n=10): VF was untreated for 8 min followed by 8 min of CPR; (3) sham control group (n=5): a sham operation was performed without VF induction and CPR. Intestinal and sublingual microcirculatory blood flow was visualized by a sidestream dark-field (SDF) imaging device at baseline and 1, 2, 4, 6, 8 h post-resuscitation. Myocardial function was measured by echocardiography and serum cytokine levels (TNF-α and IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Both intestinal and sublingual microcirculatory blood flow decreased significantly with increasing duration of cardiac arrest and resuscitation. The decreases in intestinal microcirculatory blood flow were closely correlated with the reductions of sublingual microcirculatory blood flow (perfused small vessels density: r=0.772, p<0.01; microcirculatory flow index: r=0.821, p<0.01). The decreased microcirculatory blood flow was closely correlated with weakened myocardial function and elevated inflammatory cytokine levels. CONCLUSIONS: The severity of post-resuscitation intestinal microcirculatory dysfunction is closely correlated with that of myocardial function and inflammatory cytokine levels. The measurement of sublingual microcirculation reflects changes of intestinal microcirculation and may therefore provide a new option for post-resuscitation monitoring.