Effects of Atrial Natriuretic Peptide After Prolonged Hypothermic Storage of the Isolated Rat Heart

Primary graft failure (PGF) caused by ischemia‐reperfusion injury (IRI) is the strongest determinant of perioperative mortality after heart transplantation. Atrial natriuretic peptide (ANP) has been found to reduce the IRI of cardiomyocytes and may be beneficial in alleviating PGF after heart transplantation, although there is a lack of evidence to support this issue. The purpose of this study was to investigate the cardioprotective effects of ANP after prolonged hypothermic storage. For this purpose, an isolated working‐heart rat model was used. After the preparation, the hearts were arrested with and stored in an extracellular‐based cardioplegic solution at 3–4°C for 6 h and followed by 25 min of reperfusion. The hearts were divided into four groups (n = 7 in each group) according to the timing of ANP administration: Group 1 (in perfusate before storage), Group 2 (in cardioplegia), Group 3 (in reperfusate), and control (no administration of ANP). Left ventricular functional recovery and the incidence of ventricular fibrillation (VF) were compared. ANP administration at the time of reperfusion improved the percent recovery of left ventricular developed pressure (control, 45.5 ± 10.2; Group 1, 47.4 ± 8.8; Group 2, 45.3 ± 12 vs. Group 3, 76.3 ± 7; P < 0.05) and maximum first derivative of the left ventricular pressure (control, 47.9 ± 8.7; Group 1, 46.7 ± 8.8; Group 2, 49.6 ± 10.8 vs. Group 3, 76.6 ± 7.5; P < 0.05). The incidence of VF after reperfusion did not differ significantly among these four groups (71.4, 85.7, 57.1, and 85.7% in Groups 1, 2, 3, and control, respectively). This result suggests that the administration of ANP at the time of reperfusion may have the potential to decrease the incidence of PGF after heart transplantation.     

The effects of Na+ -H+ exchange inhibitor, KB-R9032, administered at the time of reperfusion in perfused rat heart

BACKGROUND: We have reported that pretreatment with KB-R9032, a newly developed Na+ -H+ exchange inhibitor is protective against reperfusion-induced ventricular arrhythmia in the isolated perfused rat heart. This study was conducted to elucidate whether the drug is equally effective when it is given at the time of reperfusion. METHODS: Male Wistar rat hearts (n=32, 16 for each group) were perfused by means of Langendorff technique. Each heart was subjected to regional ischemia (occlusion of the left anterior descending coronary artery for 11 minutes) and to three minutes of reperfusion (release of the occlusion). KB-R9032 4 mg (one shot group) or a vehicle without drug (control) were given 30 seconds before the reperfusion to 30 seconds after the reperfusion. RESULTS: In the control group reperfusion-induced ventricular fibrillation (VF) occurred in 91.7% and the duration was 165 +/- 14.4 seconds, but, in one shot group, the incidence of VF decreased to 6.3% and the duration of VF was reduced to 0.4 +/- 0.4 seconds, respectively (P<0.05 vs control group). CONCLUSIONS: It has been shown in this study that the Na+/H+ exchange inhibitor KB-R9032 given at the time of reperfusion suppresses reperfusion arrhythmias in the ischemia-reperfusion model of isolated rat heart.     

Ischemic postconditioning: brief ischemia during reperfusion converts persistent ventricular fibrillation into regular rhythm

Objectives: Brief episodes of myocardial ischemia-reperfusion employed during reperfusion after a prolonged ischemic insult may attenuate the total ischemia-reperfusion injury. This phenomenon has been termed ischemic postconditioning. In the present study, we studied the possible effect of postconditioning on persistent reperfusion-induced ventricular fibrillation (VF) in the isolated rat heart model. Methods: Isolated Langendorff-perfused rat hearts (n=46) were subjected to 30 min of regional ischemia and reperfusion. The hearts with persistent VF (n=11) present after 15 min of reperfusion were then randomly assigned into one of the two groups: (1) control hearts (n=6), in which perfusion was continued without intervention; (2) postconditioned hearts (n=5) subjected to 2 min of global ischemia followed by reperfusion. Left ventricular pressures, heart rate, coronary flow, and electrogram were monitored throughout the experiment. Results: Conversion of VF into regular rhythm was observed in all hearts subjected to postconditioning. Regular beating was maintained by all postconditioned hearts during the subsequent reperfusion. None of the hearts in the control group had normal rhythm at the end of the experiment. At the end of reperfusion, the left ventricular developed pressure was lower in beating postconditioned hearts compared to the hearts that did not develop persistent VF. Conclusions: Ischemic postconditioning possesses strong antiarrhythmic effect against persistent reperfusion-induced tachyarrhythmias. Postconditioning may be an interesting, novel adjunct strategy to protect the heart.     

Influence of Timing of Administration on the Analgesic Effect of Bupivacaine Infiltration in Carrageenin-injected Rats

Background: Recent evidence has suggested that the timing of administration of analgesic drugs could influence their efficacy by reducing the sensitization of the nervous system induced by the nociceptive inputs, but this concept of preemptive analgesia is still debated in both clinical and basic research.

Methods: The model of acute inflammatory pain induced by carrageenin was used to study the influence of timing of administration of bupivacaine (0.2 ml of a 0.5% solution with 0.005 mg/ml epinephrine) on the development of hyperalgesia, edema, and increase in temperature. The animals received bupivacaine 5 min before (BUPI PRE group, n = 20) or 60 min after (BUPI POST group, n = 20) carrageenin (1 ml/kg of 1% solution) was injected into the left hind paw. Two control groups (n = 15 in each) received saline 5 min before or 60 min after administration of carrageenin. Hyperalgesia of the injected paw was evaluated by the vocalization threshold to paw pressure, edema by measuring paw circumference with a thread, and plantar temperature with a thermocouple thermometer. All measurements were done before carrageenin injection then every 30 min thereafter for 240 min. Another series (n = 24), with the same four groups was also evaluated at 24 h.

Results: Local injection of bupivacaine 60 min after carrageenin partially reduced the edema and hyperalgesia. The injection of bupivacaine 5 min before carrageenin was more efficient than the delayed injection and reduced hyperalgesia, edema and the increase in temperature temporarily, but did not totally prevent their development. All groups were similar at 240 min and 24 h.     

Reduced release of vasoconstrictors from the porcine heart after repeated periods of ischemia

OBJECTIVE: To examine if the decline in post-ischemic hyperemic flow after repeated brief periods of myocardial ischemia is accompanied by augmented cardiac release of the vasoconstrictors endothelin-1 (ET-1) and norepinephrine (NE). DESIGN: Mid-LAD (left anterior descending coronary artery) was occluded for 10 min with 30 min intervals a total of four times in six anesthetized pigs. Blood from the anterior interventricular coronary vein was drained through a shunt to the right atrium to facilitate blood sampling. Plasma concentrations of ET-1 and NE were repeatedly measured in arterial and coronary venous blood to estimate cardiac vasoconstrictor release. RESULTS: Plasma concentrations of ET-1 and NE remained unaltered, but cardiac release of both vasoconstrictors rose briefly during reperfusion due to the hyperemia. However, release declined progressively after repeated periods of ischemia and reperfusion and amounted to 53% (NE) and 17% (ET-1) of initial release after the fourth period of ischemia. CONCLUSION: The decline in post-ischemic hyperemia after repeated brief periods of myocardial ischemia is not accompanied by a progressive accentuation of cardiac ET-1 and NE release.     

Transient occlusion of the left anterior descending coronary artery in pigs

The purpose of this study was to define a model of transient coronary occlusion (CO) in the open-chest pig. The left anterior descending (LAD) coronary artery was occluded at its mid-length in 45 white pigs and reperfusion was performed after 30, 45, 60 or 90 min. One group of 9 animals with permanent CO served as control. During the occlusion period only slight hemodynamic changes were observed, but a period of ventricular arrhythmias was consistently observed between 15 and 30 min after CO, with an incidence of ventricular fibrillation (VF) in 8 cases (18%). All but 1 of the animals with VF could be defibrillated in less than 1 min or 3 electrical countershocks. Complex arrhythmias with marked hypotension were consistently observed after reperfusion. Histological examination showed a patent coronary artery lumen and minor changes in the LAD coronary artery at the site of occlusion in the reperfused animals and completely occluded arteries in the control group. Two pigs (4.4%) died during the night following CO. Transient CO can be performed safely in pigs with a very low complication rate and a high 24-hour survival rate.     

Beneficial effects of sevoflurane and desflurane against myocardial reperfusion injury after cardioplegic arrest

PURPOSE: To determine whether sevoflurane or desflurane offer additional protective effects against myocardial reperfusion injury after protecting the heart against the ischemic injury by cardioplegic arrest. METHODS: Isolated rat hearts in a Langendorff-preparation (n = 9) were arrested by infusion of HTK cardioplegic solution and subjected to 30 min global ischemia followed by 60 min reperfusion (controls). An additional 18 hearts were subjected to the same protocol, and sevoflurane (n = 9) or desflurane (n = 9) was added to the perfusion medium during the first 30 min of reperfusion in a concentration corresponding to 1.5 MAC in rats. Left ventricular (LV) developed pressure and creatine kinase (CK) release were determined as indices of myocardial performance and cellular injury, respectively. RESULTS: The LV developed pressure recovered to 46+/-7% of baseline in controls. Functional recovery during reperfusion was improved by inhalational anesthetics to 67+/-3% (sevoflurane, P<0.05) and 61+/-5% of baseline (desflurane, P<0.05), respectively. Peak CK release during early reperfusion was reduced from 52+/-11 U x min(-1) x g(-1) in controls to 34+/-7 and 26+/-7 U x min(-1) x g(-1) in sevoflurane and desflurane treated hearts, respectively. The CK release during the first 30 min of reperfusion was reduced from 312+/-41 U x g(-1) in control hearts to 195+/-40 and 206+/-37 U x g(-1) in sevoflurane and desflurane treated hearts. CONCLUSION: After ischemic protection by cardioplegia, sevoflurane and desflurane given during the early reperfusion period offer additional protection against myocardial reperfusion injury.     

Continuous infusion of magnesium–lidocaine mixture for prevention of ventricular arrhythmias during on-pump coronary artery bypass grafting surgery

BackgroundDuring on-pump coronary artery bypass grafting (CABG) surgery, the incidence of reperfusion ventricular fibrillation (VF) is high and post-bypass ventricular arrhythmias are common. Both reperfusion VF and ventricular arrhythmias can cause additional myocardial injury to the already ischemic myocardium. This trial aimed to test the assumption that continuous combined magnesium and lidocaine infusion would be efficient and long lasting for the prevention of post-myocardial vascularization ventricular arrhythmias including VF.MethodsEighty ASA III patients, who were candidates for CABG surgery, were randomly assigned into two groups: Group I (control group, n = 40) and Group II (Group ML, n = 40). After endotracheal intubation, patients of control group were infused with plain normal saline in a volume equivalent to study drugs’ mixture volume. Patients of Group ML were infused with magnesium–lidocaine mixture to achieve a bolus of magnesium sulfate 2 g and lidocaine 100 mg followed by continuous infusion of Mg sulfate 500 mg/h and lidocaine 1 mg/min. The initial cardiac rhythm after aortic cross clamp (ACC) release and the occurrence of post-CPB significant ventricular arrhythmias were recorded.ResultsThe incidences of reperfusion VF and post-CPB ventricular arrhythmias in Group ML were significantly lower than that in control group (22.5% vs. 72.5%) (P < 0.001) and (7.5% vs. 25%) (P < 0.05), respectively. However, in Group ML, this beneficial effect was associated with higher incidence of sinus bradycardia (72.5% vs. 17.5%) and hence pacing needs (22.5% vs. 0.0%) when compared with control group.ConclusionOur study concluded that, during on-pump CABG surgery, the combined administration of magnesium and lidocaine as a bolus dose starting after intubation followed by continuous infusion reduced the incidence of reperfusion VF by 62% and post-CPB ventricular arrhythmias by 70% on expense of increased the incidence of sinus bradycardia and pacing.     

Adenosine preconditioning reduces both pre and postischemic arrhythmias in human myocardium

INTRODUCTION: Consistently, clinical series record supraventricular tachyarrhythmias in approximately 30% of patients following coronary artery bypass surgery (CABG). Ischemic preconditioning and adenosine preconditioning (Ado-PC) decrease postischemia/reperfusion (I/R) myocardial stunning, infarct size, and pharmacologically induced arrhythmias in all species including man. We hypothesized that adenosine preconditioning would decrease spontaneous pre- and postischemic atrial arrhythmias in human myocardium. The purposes of this study were to determine the effect of in vivo and in vitro Ado-PC on atrial arrhythmias. METHODS: Human atrial trabeculae were harvested from CABG patients, placed in organ baths, and paced (1 Hz). Developed force (DF) was recorded during simulated I/R (30/45 min). Prior to I/R, trabeculae were treated with Ado (125 microM) for 5 min (in vitro), or patients were treated with Ado (12 mg iv) 5 min (in vivo) prior to harvest of trabeculae. Contraction frequency >4 Hz (defined as atrial tachyarrhythmias) was recorded in all groups pre- and postischemia. RESULTS: Control trabeculae exhibited increased tachyarrhythmias pre- and postischemia. In vivo and in vitro Ado-PC suppressed both pre- and postischemic arrhythmias. CONCLUSIONS: Adenosine preconditioning suppresses the frequency of pre- and postischemic tachyarrhythmias against an ischemia/reperfusion insult in human myocardium. This antiarrhythmic effect occurs with both in vitro and in vivo administration of adenosine. Preconditioning with adenosine prior to elective ischemia/reperfusion is a promising strategy of reducing spontaneous atrial arrhythmias in patients undergoing myocardial revascularization.     

2-Nicotinamidoethyl nitrale (2-NN) protects myocardium in ischemia and reperfusion via the protein kinase C pathway

BACKGROUND: Several recent studies have suggested an ATP-sensitive potassium channel opener (2-nicotinamidoethyl nitrate: 2-NN) may exert a protective effect against the myocardial ischemic/reperfusion injury. This study examines the effects of 2-NN on intracellular signaling by measuring intracellular cyclic AMP, cyclic GMP accumulation and protein kinase C (PKC) activity after 2-NN perfusion. METHODS: Ischemia/reperfused hearts were made by LAD occlusion for 30 min followed by 30 min of reperfusion in isolated rat hearts. Hearts were pre-perfused with 0.1 mM 2-NN, 100 nM Calphostin C, or 2-NN plus Calphostin C for 10 min prior to ischemia. The left ventricular function, cyclic AMP, cyclic GMP and LDH were examined to determine the effects of 2-NN on ischemic/reperfusion injury. Four separate groups of hearts were stained with a bisindolylmaleimide PKC inhibitor conjugated to fluorescein (fim, Teflabs) and PKC activity was measured. RESULTS: 2-NN reduced ischemia/reperfusion injury as evidenced by the enhanced myocardial functional recovery, decreased LDH release after reperfusion, and decreased reperfusion arrhythmias. The PKC inhibitor attenuated myocardial functional recovery but not reperfusion arrhythmias. Cyclic AMP levels decreased after 10 min of 2-NN perfusion, compared to controls. We observed an increase in PKC activity after 2-NN treatment. CONCLUSIONS: These results suggest that PKC plays a significant role in the cardioprotective effect of 2-NN on ischemic and reperfused myocardium. The anti-arrhythmic effect of 2-NN in the reperfusion phase may be linked its action on the ATP-sensitive potassium channel itself rather than its effect on PKC activity.     

Effects of ketamine and its isomers on ischemic preconditioning in the isolated rat heart

BACKGROUND: Ischemic preconditioning protects the heart against subsequent ischemia. Opening of the adenosine triphosphate-sensitive potassium (KATP) channel is a key mechanism of preconditioning. Ketamine blocks KATP channels of isolated cardiomyocytes. The authors investigated the effects of ketamine and its stereoisomers on preconditioning. METHODS: Isolated rat hearts (n = 80) underwent 30 min of no-flow ischemia and 60 min of reperfusion. Two groups with eight hearts each underwent the protocol without intervention (control-1 and control-2), and, in eight hearts, preconditioning was elicited by two 5-min periods of ischemia before the 30 min ischemia. In the six treatment groups (each n = 8), ketamine, R(-)- or S(+)-ketamine were administered at concentrations of 2 or 20 microg/ml before preconditioning. Eight hearts received 20 microg/ml R(-)-ketamine before ischemia. Left ventricular (LV) developed pressure and creatine kinase (CK) release during reperfusion were determined as variables of ventricular function and cellular injury. RESULTS: Baseline LV developed pressure was similar in all groups: 104 +/- 28 mmHg (mean +/- SD). Controls showed a poor recovery of LV developed pressure (17 +/- 8% of baseline) and a high CK release (70 +/- 17 IU/g). Ischemic preconditioning improved recovery of LV developed pressure (46 +/- 14%) and reduced CK release (47 +/- 17 IU/g, both P < 0.05 vs. control-1). Ketamine (2 microg/ml) and 2 or 20 microg/ml S(+)-ketamine had no influence on recovery of LV developed pressure compared with preconditioning (47 +/- 18, 43 +/- 8, 49 +/- 36%) and CK release (39 +/- 8, 30 +/- 14, 41 +/- 25 IU/g). After administration of 20 microg/ml ketamine and 2 or 20 microg/ml R(-)-ketamine, the protective effects of preconditioning were abolished (LV developed pressure-recovery, 16 +/- 14, 22 +/- 21, 18 +/- 11%; CK release, 67 +/- 11, 80 +/- 21, 82 +/- 41 IU/g; each P < 0.05 vs. preconditioning). Preischemic treatment with R(-)-ketamine had no effect on CK release (74 +/- 8 vs. 69 +/- 9 IU/g in control-2, P = 0.6) and functional recovery (LV developed pressure 12 +/- 4 vs. 9 +/- 2 mmHg in control-2, P = 0.5). CONCLUSION: Ketamine can block the cardioprotective effects of ischemic preconditioning. This effect is caused by the R(-)-isomer.     

Effects of Ketamine and Its Isomers on Ischemic Preconditioning in the Isolated Rat Heart

Background: Ischemic preconditioning protects the heart against subsequent ischemia. Opening of the adenosine triphosphate-sensitive potassium (KATP) channel is a key mechanism of preconditioning. Ketamine blocks KATP channels of isolated cardiomyocytes. The authors investigated the effects of ketamine and its stereoisomers on preconditioning.

Methods: Isolated rat hearts (n = 80) underwent 30 min of no-flow ischemia and 60 min of reperfusion. Two groups with eight hearts each underwent the protocol without intervention (control-1 and control-2), and, in eight hearts, preconditioning was elicited by two 5-min periods of ischemia before the 30 min ischemia. In the six treatment groups (each n = 8), ketamine, R (-)- or S (+)-ketamine were administered at concentrations of 2 or 20 [mu]g/ml before preconditioning. Eight hearts received 20 [mu]g/ml R (-)-ketamine before ischemia. Left ventricular (LV) developed pressure and creatine kinase (CK) release during reperfusion were determined as variables of ventricular function and cellular injury.

Results: Baseline LV developed pressure was similar in all groups: 104 +/- 28 mmHg (mean +/- SD). Controls showed a poor recovery of LV developed pressure (17 +/- 8% of baseline) and a high CK release (70 +/- 17 IU/g). Ischemic preconditioning improved recovery of LV developed pressure (46 +/- 14%) and reduced CK release (47 +/- 17 IU/g, both P < 0.05 vs. control-1). Ketamine (2 [mu]g/ml) and 2 or 20 [mu]g/ml S (+)-ketamine had no influence on recovery of LV developed pressure compared with preconditioning (47 +/- 18, 43 +/- 8, 49 +/- 36%) and CK release (39 +/- 8, 30 +/- 14, 41 +/- 25 IU/g). After administration of 20 [mu]g/ml ketamine and 2 or 20 [mu]g/ml R (-)-ketamine, the protective effects of preconditioning were abolished (LV developed pressure-recovery, 16 +/- 14, 22 +/- 21, 18 +/- 11%; CK release, 67 +/- 11, 80 +/- 21, 82 +/- 41 IU/g; each P < 0.05 vs. preconditioning). Preischemic treatment with R (-)-ketamine had no effect on CK release (74 +/- 8 vs. 69 +/- 9 IU/g in control-2, P = 0.6) and functional recovery (LV developed pressure 12 +/- 4 vs. 9 +/- 2 mmHg in control-2, P = 0.5).     

The cardioprotective effects of thoracal epidural anestesia are induced by the expression of vascular endothelial growth factor and inducible nitric oxide synthase in cardiopulmonary bypass surgery

AIM: The cardioprotective effects of thoracal epidural anesthesia (TEA) are induced by the expression of vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (i-NOS) in cardiopulmonary bypass (CPB) surgery. When general anaesthesia (GA) is combined with TEA during coronary artery bypass graft, we investigated whether TEA together with GA play a role on VEGF and i-NOS expression in human heart tissue in cardiac ischemia. METHODS: Right atrial biopsy samples were taken before CPB, before aortic cross clamp (ACC) and at 15 min after ACC release (after ischemia and reperfusion). Human heart tissues were obtained from the TEA+GA and GA groups. Immunocytochemistry was performed using antibodies for VEGF and i-NOS. RESULTS: Both VEGF and i-NOS immunoreactivity was observed in cardiomyocytes and arteriol walls. Although VEGF and i-NOS immunoreactivity was apparent in both groups,, immunostaining intensity was greater in the TEA+GA group than the GA group. Between groups, at 4 h and at 24 h after the end of CPB, the cardiac index (CI) was significantly higher in the TEA+GA group than GA group (3.4+/-0.8 L/min/m(2) vs 2.5+/-0.8 L/min/m(2); P<0.001), (3.8+/-1.1 L/min/m(2) vs 3.1+/-1.1 L/min/m(2); P<0.008) respectively. Within groups, at 4 and 24 h after the end of CPB, the CI was significantly higher in the TEA+GA group than baseline values, (3.4+/-0.8 L/min/m(2) vs 2.4+/-0.7 L/min/m(2); P<0.001), (3.8 +/-1.1 L/min/m(2) vs 2.4+/-0.7 L/min/m(2); P<0.001) respectively, but no difference was found in the GA group (2.6+/-0.8 L/min/m(2) vs 2.5+/-0.8 L/min/m(2); P>0.05), (2.6+/-0.8 L/min/m(2) vs 3.1+/-1.1 L/min/m(2); P>0.05) respectively. After ACC release, 11/40 (27.5%) patients in the TEA+GA group showed ventricular fibrillation (VF), atrial fibrillation or heart block versus 25/40 (62.5%) of those in the GA group. VF after ACC release in the TEA+GA group (9/20 patients, 22.5%) was significantly lower than in the GA group (21/40 patients, 52.5%); (P<0.006). Sinus rhythm after ACC release in the TEA+GA group (29/40 patients, 72.5%) was significantly higher than in the GA group (15/40 patients, 37.5%); (P<0.002). CONCLUSIONS: The results of the present study indicate that TEA plus GA in coronary surgery preserve cardiac function via increased expression of VEGF and i-NOS, improved hemodynamic function and reduced arrhythmias after ACC release.     

Comparison of effects of verapamil and those of nicardipine on myocardial ischemia and reperfusion injury: a study in an in situ rabbit model]

This study was designed to investigate whether two L-type calcium antagonists, verapamil and nicardipine reduce the myocardial necrosis (infarct size) following ischemia and reperfusion. Rabbits (n = 52) were subjected to regional myocardial ischemia by 30 min of the left anterior descending artery occlusion followed by 3 hrs of reperfusion under ketamine/xylazine anesthesia. The animals were randomly assigned to a control group, and verapamil or nicardipine treatment groups. A continuous infusion of verapamil (0.1 mg.kg-1.h-1) or nicardipine (0.06 mg.kg-1.h-1) was initiated 5 min prior to ischemia, immediately after ischemia, 5 min after ischemia, 5 min prior to reperfusion, immediately after reperfusion, and 5 min after reperfusion. A lead II ECG was recorded throughout the experiment for determining ventricular arrhythmias. The area at risk was delineated by Evans blue, and infarct size was determined by triphenyl tetrazolium chloride staining at the end of the experiment in the heart (the left anterior descending artery was religated). The area at risk showed no significant differences among all the groups tested; infarct size in the rabbits to which verapamil was given 5 min before subjecting to ischemia was significantly reduced to 41.7 +/- 4.3% from 65.9 +/- 1.7% in control rabbits. The treatment with nicardipine at any period of time did not reduce infarct size. On the other hand, the incidence of reperfusion-induced arrhythmias was decreased by nicardipine infusion, when started 5 min prior to ischemia, immediately after ischemia, 5 min after ischemia, 5 min prior to reperfusion, and immediately after reperfusion. These results suggest that verapamil given before coronary artery occlusion has an infarct limiting effect in the myocardium, and that nicardipine has an antiarrhythmic effect during reperfusion in the rabbit heart.     

Effects of adenosine infusion on the pig heart during normothermic ischemia and reperfusion.

Possible enhancement of myocardial protection during ischemia and reperfusion by administration of adenosine was evaluated in a pig heart model. Adenosine (100 micrograms/kg/min) was infused into the aortic root during ischemia in group AI (n = 5) and into the right atrium during reperfusion in group AR (n = 6). Group C (n = 6) served as controls. During cardiopulmonary bypass the hearts were subjected to 30 min of normothermic ischemia and 15 min of reperfusion before weaning. In group AI the stroke work index 30 and 90 min after ischemia and the mean arterial pressure 30 min after ischemia were significantly higher than in group C. These parameters did not differ significantly between groups AR and C. All groups showed decrease in myocardial adenosine triphosphate (ATP) and adenylate charge potential (ACP) during ischemia and partial (ATP) or complete (ACP) restoration after ischemia. Adenosine infusion into the aortic root during ischemia (adenosine cardioplegia) thus resulted in improved postischemic heart function, although biochemical correlates in ATP and ACP were not apparent.     

Can preconditioning reduce laparoscopy-induced tissue injury?

Background: Pneumoperitoneum (P) created to facilitate laparoscopy (L) is associated with splanchnic perfusion, ischemia/reperfusion (I/R) injury, and oxidative stress. In this randomized controlled experimental study with blind outcome assessment, we evaluated the effect of preconditioning (PRE) on L-induced I/R injury. Methods: The subjects were 40 Sprague-Dawley male rats. P was created in all except controls, using carbondioxide (CO₂) insufflation under a pressure of 15 mmHg. PRE consisted of 10 min of P, followed by 10 min of deflation (D). The rats were randomized to the following groups: Group P was subjected to 60 min of P. Group P/D was subjected to 60 min of P, followed by 45 min of D. Group PRE/P was subjected to PRE, followed by 60 min of P. Group PRE/P/D was subjected to PRE, followed by 60 min of P and 45 min of D. Group C (control) was subjected to a sham operation, without P. Its anesthesia time was equal to that for group PRE/P/D. At the end of the experiments, the rats were killed; blood, liver, and kidney samples were then obtained and coded. Plasma alanine aminotransferase (ALT) and malondialdehyde (MDA), as well as homogenized tissue MDA levels and glutathione (GSH) activities, were measured; tissue samples were assessed for histopathological evidence of injury; all assessments were done by investigators blinded to the study design. The results were decoded and analyzed statistically with the Kruskal-Wallis and Mann Whitney tests. A p < 0.05 was considered significant. Results: Plasma ALT as well as plasma, liver, and kidney MDA levels and liver and kidney injury scores were increased, whereas liver and kidney GSH values were decreased in groups P and P/D, as compared to group C. Rats subjected to PRE before P had plasma ALT, kidney MDA, and kidney and liver GSH levels comparable to controls; their kidney and liver injury scores were higher than controls but significantly lower than nonpreconditioned animals. PRE enabled decreased plasma, kidney, and liver MDA as well as increased kidney GSH if applied before P; its efficacy on oxidative stress was limited to providing decreased kidney MDA and increased kidney GSH if applied before P/D. However, PRE significantly attenuated kidney and liver injury after P as well as P/D. Conclusion: PRE consisting of 10 min of P followed by 10 min of D decreases the oxidative stress induced by sustained P in the plasma, liver, and kidney. PRE significantly limits liver and kidney injury after prolonged P and P/D. After further studies to define its ideal timing, PRE before L incorporating P may have clinical relevance, especially for elderly patients or those with impaired hepatic and/or renal function or perfusion. Presented in poster format at the 10th International Congress of the European Association for Endoscopic Surgery (E.A.E.S.), Libson, Portugal, 2–5 June 2002     

Effects of different steroid treatment on reperfusion-associated production of reactive oxygen species and arrhythmias during coronary surgery

BACKGROUND: During conventional cardiac surgery ischemia and reperfusion may cause excessive production of reactive oxygen species leading to tissue damage including early arrhythmias. We therefore assessed the kinetics of markers of radical stress including oxidized and reduced glutathione (GSSG/GSH), oxidized proteins (PCG) and malondialdehyde (MDA), and tested the hypothesis that different steroid treatments inhibit these markers and early reperfusion-associated supraventricular and ventricular extrasystolic beats. METHODS: In a randomized, controlled, blinded, prospective trial 36 patients received a preoperative infusion of methylprednisolone (MP, 15 mg kg-1, n = 12), tirilazad mesylate (TM, 10 mg kg-1, n = 12) or placebo (PL, NaCl, n = 12). Coronary sinus and arterial blood was drawn at baseline and 2, 5, 15, 30, 60 and 240 min after aortic declamping. Holter-ECG analysis was used to identify arrhythmias. RESULTS: Cardiac GSSG release occurred very early (< 15 min) and was not significantly attenuated by either drug treatment. Cardiac PCG production showed biphasic increases, lasted > 4 h and was significantly reduced only by TM. Cardiac MDA release was short (< 30 min) and significantly reduced by MP and TM. Neither treatment had a significant influence on the early occurrence of ventricular or supraventricular arrhythmias. The number of patients needing cardioversions or defibrillations also were not different. CONCLUSIONS: The results indicate that cardiac production of reactive oxygen species occurs after reperfusion in humans and is not inhibited by steroid treatment. Steroid treatment effectively reduces lipid peroxidation during cardiac surgery but has no influence on arrhythmias.     

Atropine before Enflurane Anaesthesia: Effects on Cardiac Rhythm, Pulse Rate, Blood Pressure and Airway Secretion

The occurrence of cardiac arrhythmias and changes in pulse rate and blood pressure during mask anaesthesia with enflurane was investigated in 92 patients with special reference to the influence of atropine (0.01 mg kg-1 5 min before anaesthesia) and thiopental. The average duration of anaesthesia was a little less than 1 h in all four groups. More than five ventricular extrasystoles occurred in one patient (38 min after atropine). Supraventricular (mainly nodal) arrhythmias were significantly (P less than 0.005) more common in the atropine groups (15/45) than in the non-atropine groups (4/47). Following atropine, heart rate increased by about 25 beats min-1, whereas only very slight increases were seen in the non-atropine groups. Blood pressure fell at the induction but was almost back to normal at the end of anaesthesia. Blood pressure was unaffected by atropine. Slightly lower values of blood pressure were suggested in the thiopental groups, whereas thiopental did not modify cardiac rhythm or pulse rate. Suction of the pharynx was necessary in only one patient. In conclusion, the present study does not support the routine administration of atropine before enflurane anaesthesia with or without thiopental induction.     

Efficacy of a hydroxyl radical scavenger (VF 233) in preventing reperfusion injury in the isolated rabbit heart.

We tested the hypothesis that 3,4,5,-trihydroxybenzamidoxime (VF 233), a demonstrated hydroxyl radical scavenger and an effective Fe3+ chelator, attenuates reperfusion injury and improves isovolumic left ventricular function. Eighteen isolated, perfused rabbit hearts with intracavitary balloons were subjected to normothermic, global ischemia until the initiation of ischemic contracture. Effects on the adenine nucleotide pool metabolites were determined by high-pressure liquid chromatography from right ventricular biopsy specimens before ischemia and at 15-minute intervals throughout reperfusion. In the experimental group (n = 9), a 5-mL bolus of 1 mol/L VF 233 was given immediately before reperfusion and followed by a continuous infusion (0.125 mumol/min). The control group (n = 9) received the vehicle solution at identical times. Rabbits treated with VF 233 had significant improvement in left ventricular function (expressed as percent return of left ventricular peak developed pressure) within 15 minutes of reperfusion (55.0 +/- 3.0 versus 66.2 +/- 4.1; p less than 0.05 by analysis of variance) after global ischemia and remained significantly improved throughout the reperfusion period. Myocardial adenine nucleotide pool intermediates were not significantly different between groups. These results demonstrate that administration of VF 233 significantly improves ventricular function but does not affect adenine nucleotide metabolism after ischemia and reperfusion.     

Effect of intraarterial, intraportal or combined norepinephrine infusion on hemorrhage at experimental liver trauma in the rat

The effect of intraarterial, intraportal or simultaneous intraarterial and intraportal norepinephrine (NE) infusion on hemorrhage after standardized liver trauma was evaluated in the rat. Infusion of NE through a catheter in the gastroduodenal artery or/and vein, was started 5 min prior to the liver trauma and continued throughout the experiment. Blood pressure was continuously registered after cannulation of the femoral artery. Standardized liver trauma involved resection of the left anterior liver lobe. Bleeding time, blood loss from the traumatized liver surface, hemoglobin (Hb), hematocrit (Hct), platelet count (PC) and white blood cell count (WBC) were measured. Infusion of NE resulted in significant increase of blood pressure compared with controls. Infusion of NE (i.a., i.p., i.a. + i.p.) caused significant decrease in bleeding time and blood loss. Hb, Hct, PC and WBC were not affected. NE infusion proved effective in decreasing hemorrhage at liver trauma; the route of administration did not influence the results.