Effects of ischemic preconditioning and synchronized coronary venous retroperfusion in an off-pump coronary artery bypass grafting model

Off-pump coronary artery bypass grafting (CABG) has become a popular procedure. However, temporary occlusion of the target vessel is sometimes a threat to the patients. Although ischemic preconditioning (IP) has been proposed to reduce myocardial injury, its effects remain controversial. The coronary veins represent an alternate route for delivery of therapeutic agents and arterial blood to the acutely ischemic myocardium. The aim of this study was to investigate the protective effect against myocardial ischemia and reperfusion injury of combined IP and synchronized coronary venous retroperfusion (SCVR) in an off-pump CABG model. Twenty-one pigs were assigned to 3 groups of 7 animals. In the control group, the left anterior descending coronary artery (LAD) was occluded for 45 min followed by 2 h of reperfusion using a left intrathoracic artery (LITA) bypass circuit. In the IP group, LAD occlusion was done for 5 min with 15 min of reperfusion, followed by 45 min of LAD occlusion. In the SCVR group, pretreatment before LAD occlusion was the same as in the IP group. Then, SCVR was commenced just after the start of LAD occlusion for 45 min. The percent systolic shortening of ischemic myocardium (measured by sonomicrometry) after reperfusion via the LITA was significantly (p < 0.001) greater in the SCVR group (14.6 +/- 3.3%) than in the control group (-1.6 +/- 5.6%, 95%CI: -24.3 - -8.1) or the IP group (0.7 +/- 8.0%, 95%CI: -22.0 - -5.8) after 30 min of reperfusion, and this difference persisted throughout the reperfusion period. Infarct size (expressed as a percentage of the area at risk) was significantly (p < 0.001) smaller in the SCVR group (2.4 +/- 2.7%) than in the control group (83.0 +/- 2.3%, 95%CI: -99.0 - -62.4) or the IP group (42.0 +/- 23.0%, 95%CI: -58.0 - -21.3). Combined SCVR and IP had a potent myocardial protective effect in the present off-pump CABG model. This method may be clinically feasible and may be able to prolong a safe coronary occlusion.     

Mechanism of Myocardial Protection by Isoflurane: Role of Adenosine Triphosphate-regulated Potassium (K sub ATP) Channels

Background: The mechanism of the protective actions of volatile anesthetics in ischemic myocardium has not been clearly elucidated. The role of myocardial adenosine triphosphate-regulated potassium (KATP) channels in isoflurane-induced enhancement of recovery of regional contractile function after multiple brief occlusions and reperfusion of the left anterior descending coronary artery (LAD) was studied in dogs anesthetized with barbiturates.

Methods: Dogs (n = 32) were instrumented to measure left ventricular and aortic blood pressure, cardiac output, LAD coronary blood flow velocity, and subendocardial segment length. Regional myocardial perfusion was measured using radioactive microspheres. Hemodynamics and percentage segment shortening (%SS) in the LAD perfusion territory were evaluated after instrumentation was complete; after pretreatment with the KATP channel antagonist, glyburide (0.05 mg/kg sup -1) or drug vehicle (polyethylene glycol in ethyl alcohol; control experiments); and in the presence or absence of 1 MAC isoflurane administered for 30 min before and during five 5-min occlusions and reperfusion of the LAD in four experimental groups. Isoflurane was discontinued at the onset of the final reperfusion period. Measurements of hemodynamics, %SS, and myocardial perfusion were repeated at several intervals during 180 min after reperfusion of the LAD.

Results: Left anterior descending coronary artery occlusion caused regional dyskinesia during each 5-min occlusion in each dog. Control and glyburide-pretreated dogs demonstrated poor recovery of %SS by 180 min after reperfusion (2 +/- 10 and 7 +/- 6% of baseline, respectively). In contrast, dogs anesthetized with isoflurane exhibited complete recovery of function (%SS) by 180 min after reperfusion (82 +/- 8% of baseline). Enhanced recovery of regional contractile function by isoflurane was abolished by pretreatment with glyburide 180 min after reperfusion (16 +/- 10% of baseline). Improvement of functional recovery of stunned myocardium by isoflurane, and the blockade of this action by glyburide, was not associated with changes in hemodynamics or regional myocardial perfusion.     

Transmyocardial laser treatment reduces ischemia-induced ventricular fibrillation during the early phase (1a) after coronary artery occlusion in open chest anesthetized pigs

INTRODUCTION: It has previously been shown that transmyocardial revascularization with laser (TMR) prior to coronary artery occlusion decreases the occurrence of ischemia-induced arrhythmias. The aim of the present study was to determine the effects of TMR on ventricular fibrillation and other arrhythmias during the early (1a) and late phase (1b) of ischemia in pigs. METHODS: In six pigs TMR was performed in the anterior wall of the left ventricle 60 minutes prior to occlusion of the proximal LAD. Six other pigs were subjected to coronary occlusion without preceding TMR and served as controls. RESULTS: During the 30 min period with LAD occlusion ventricular fibrillation occurred 22 times in 5 of 6 control animals (20 episodes in phase la, 2 in phase 1b), whereas none of the animals subjected to TMR prior to the coronary artery occlusion developed ventricular fibrillation (p<0.01). The total number of premature beats per animal was lower during the early phase (la) after LAD occlusion in the TMR group than in the control group (18+/-13 vs 248+/-82, p<0.05). CONCLUSIONS: TMR prior to occlusion of LAD reduced the occurrence of early phase (la) ischemia-induced ventricular fibrillation and premature beats. This anti-fibrillatory effect might explain the improved survival observed in experimental studies after TMR prior to coronary artery occlusion found by others.     

Chemically modified tetracycline improves contractility in porcine coronary ischemia/reperfusion injury

BACKGROUND: Reperfusion of ischemic myocardium has been implicated in extension of infarct size and deleterious clinical outcomes. Anti-inflammatory agents reduce this reperfusion injury. Chemically modified tetracycline-3 (CMT-3) (Collagenex Pharmaceuticals, Newtown, PA, USA) lacks antimicrobial properties yet retains anti-inflammatory activity. We examined infarct size and myocardial function in a porcine coronary artery occlusion/reperfusion model in CMT-3-treated and control animals. METHODS: Yorkshire pigs (n = 8) underwent median sternotomy, pretreatment with heparin (300 U/kg and 67 U/kg/hr IV) and lidocaine (1 mg/kg IV) and were divided into two groups. Group one (n = 4) had the left anterior descending artery (LAD) occluded for 1 hour, after which it was reperfused for 2 hours. Group two (n = 4) had an identical protocol to group one except CMT-3 (2 mg/kg IV) was administered prior to occlusion of the LAD. RESULTS: Animals receiving CMT-3 had significantly decreased infarct size in relation to the ventricular area-at-risk (AAR) (28 +/- 9% vs. 64 +/- 8%; p < 0.05). Myocardial contractile function was superior in the CMT-3 treatment, indicated by a higher cardiac index (2.9 +/- 0.3 vs. 2.0 +/- 0.3 L/min/m(2); p < 0.05) and stroke volume index (22 +/- 2 vs. 17 +/- 1 L/m(2)/beat; p < 0.05). CONCLUSIONS: CMT-3 decreased infarct size in relation to the AAR resulting in relative preservation of contractility, suggesting CMT-3 may improve outcomes during myocardial ischemia reperfusion.     

Sevoflurane reduces myocardial infarct size and decreases the time threshold for ischemic preconditioning in dogs

BACKGROUND: Recent evidence indicates that volatile anesthetics exert protective effects during myocardial ischemia and reperfusion. The authors tested the hypothesis that sevoflurane decreases myocardial infarct size by activating adenosine triphosphate-sensitive potassium (K(ATP)) channels and reduces the time threshold of ischemic preconditioning necessary to protect against infarction. METHODS: Barbiturate-anesthetized dogs (n = 75) were instrumented for measurement of aortic and left ventricular pressures and maximum rate of increase of left ventricular pressure and were subjected to a 60-min left anterior descending (LAD) coronary artery occlusion followed by 3-h reperfusion. In four separate groups, dogs received vehicle or the K(ATP) channel antagonist glyburide (0.1 mg/kg intravenously), and 1 minimum alveolar concentration sevoflurane (administered until immediately before coronary artery occlusion) in the presence or absence of glyburide. In three additional experimental groups, sevoflurane was discontinued 30 min (memory) before the 60-min LAD occlusion or a 2-min LAD occlusion as an ischemic preconditioning stimulus was used with or without subsequent sevoflurane (with memory) pretreatment. Regional myocardial perfusion and infarct size were measured with radioactive microspheres and triphenyltetrazolium staining, respectively. RESULTS: Vehicle (23 +/- 1% of the area at risk; mean +/- SEM) and glyburide (23 +/- 2%) alone produced equivalent effects on myocardial infarct size. Sevoflurane significantly (P < 0.05) decreased infarct size (13 +/- 2%). This beneficial effect was abolished by glyburide (21 +/- 3%). Neither the 2-min LAD occlusion nor sevoflurane followed by 30 min of memory were protective alone, but together, sevoflurane enhanced the effects of the brief ischemic stimulus and profoundly reduced infarct size (9 +/- 2%). CONCLUSION: Sevoflurane reduces myocardial infarct size by activating K(ATP) channels and reduces the time threshold for ischemic preconditioning independent of hemodynamic effects in vivo.     

Sevoflurane but not propofol preserves myocardial function during minimally invasive direct coronary artery bypass surgery

Volatile anesthetics exert cardioprotective properties in experimental and clinical studies. We designed this study to investigate the effects of sevoflurane on left ventricular (LV) performance during minimally invasive direct coronary artery bypass grafting (MIDCAB) without cardiopulmonary bypass. Fifty-two patients scheduled for MIDCAB surgery were randomly assigned to a propofol or a sevoflurane group. Apart from the anesthetics used, there was no difference in surgical and anesthetic management. After determination of cardiac troponin T, creatine kinase, and creatine kinase MB, electrocardiographic (ECG) data and echocardiography variables (myocardial performance index and early to atrial filling velocity ratio) the left anterior descending coronary artery (LAD) was clamped until anastomosis with the left internal mammary artery was completed. During LAD occlusion and during reperfusion, echocardiography measurements were repeated. Blood samples were obtained repeatedly for up to 72 h. After LAD occlusion, myocardial performance index and early to atrial filling velocity ratio in the propofol group deteriorated significantly from 0.40 +/- 0.12 and 1.29 +/- 0.35 to 0.49 +/- 0.10 and 1.13 +/- 0.22, respectively, whereas there was no change in the sevoflurane group. In the propofol group myocardial performance index remained increased (0.47 +/- 0.11) compared with baseline during reperfusion. There were no significant differences in ECG and laboratory values between groups. In conclusion, during a brief period of ischemia in patients undergoing MIDCAB surgery, sevoflurane preserved myocardial function better than propofol.     

Reversal of reperfusion injury after ischemic arrest with pressure-controlled intermittent coronary sinus occlusion

Recent experimental studies have shown that pressure-controlled intermittent coronary sinus occlusion effectively reduces both infarct size and myocardium at risk after coronary artery occlusion. This study was undertaken to determine whether this modality was equally effective in altering reperfusion damage after a period of ischemic arrest. Fourteen pigs were placed on cardiopulmonary bypass and subjected to 2 hours of ischemic arrest with multidose potassium crystalloid cardioplegia supplemented with topical and systemic hypothermia (28 degrees C). During arrest, the mid-left anterior descending artery was occluded with a snare, which was released immediately after aortic unclamping. In seven pigs, a 7F balloon-tipped catheter was positioned in the coronary sinus and pressure-controlled intermittent coronary sinus occlusion was performed for 60 minutes after aortic unclamping. Seven other pigs served as controls. Parameters measured included stroke work index, ejection fraction, and myocardial pH in the distribution of the distal left anterior descending artery. Pigs treated with pressure-controlled intermittent coronary sinus occlusion had a significantly higher myocardial pH (6.99 +/- 0.06 versus 6.67 +/- 0.05, p less than 0.01), ejection fraction (50% +/- 2% versus 33% +/- 6%, p less than 0.01), and stroke work index (0.87 +/- 0.07 versus 0.61 +/- 0.05 gm-m/kg, p less than 0.01) after 60 minutes of reperfusion compared with those of the group not treated in this way. We conclude that pressure-controlled intermittent coronary sinus occlusion effectively reverses reperfusion damage after periods of ischemic arrest.     

Sevoflurane Reduces Myocardial Infarct Size and Decreases the Time Threshold for Ischemic Preconditioning in Dogs

Background: Recent evidence indicates that volatile anesthetics exert protective effects during myocardial ischemia and reperfusion. The authors tested the hypothesis that sevoflurane decreases myocardial infarct size by activating adenosine triphosphate-sensitive potassium (KATP) channels and reduces the time threshold of ischemic preconditioning necessary to protect against infarction.

Methods: Barbiturate-anesthetized dogs (n = 75) were instrumented for measurement of aortic and left ventricular pressures and maximum rate of increase of left ventricular pressure and were subjected to a 60-min left anterior descending (LAD) coronary artery occlusion followed by 3-h reperfusion. In four separate groups, dogs received vehicle or the KATP channel antagonist glyburide (0.1 mg/kg intravenously), and 1 minimum alveolar concentration sevoflurane (administered until immediately before coronary artery occlusion) in the presence or absence of glyburide. In three additional experimental groups, sevoflurane was discontinued 30 min (memory) before the 60-min LAD occlusion or a 2-min LAD occlusion as an ischemic preconditioning stimulus was used with or without subsequent sevoflurane (with memory) pretreatment. Regional myocardial perfusion and infarct size were measured with radioactive microspheres and triphenyltetrazolium staining, respectively.

Results: Vehicle (23 +/- 1% of the area at risk; mean +/- SEM) and glyburide (23 +/- 2%) alone produced equivalent effects on myocardial infarct size. Sevoflurane significantly (P < 0.05) decreased infarct size (13 +/- 2%). This beneficial effect was abolished by glyburide (21 +/- 3%). Neither the 2-min LAD occlusion nor sevoflurane followed by 30 min of memory were protective alone, but together, sevoflurane enhanced the effects of the brief ischemic stimulus and profoundly reduced infarct size (9 +/- 2%).     

Epicardial coronary artery Doppler: validation in the animal model

The aim of the study was to validate a newly-designed epicardial coronary artery Doppler probe and test its detection of changes in coronary blood flow velocity. Left anterior descending (LAD) coronary blood flow and flow velocity were evaluated in four pigs with a pericoronary transit time flow (TTF) probe and a newly-designed epicardial Doppler micro-probe. Four consecutive measurements were taken for each of the following conditions: basal, partial stenosis, occlusion, and reperfusion of the LAD. Mean TTF value (ml/min) was 23.2+/-6.6 in basal condition, 16.2+/-5.7 after partial LAD stenosis, 0.1+/-0.3 during LAD occlusion, and 67.4+/-23.3 at reperfusion (P<0.001). Similar patterns were recorded in terms of Doppler velocity (cm/s) with values of 4.0+/-1.9 in basal condition, 3.5+/-2.3 after partial LAD stenosis, 0.5+/-1.4 during LAD occlusion, and 11.1+/-5.5 at reperfusion (P<0.001). No significant differences in both TTF and Doppler velocity were detected between basal condition and partial LAD stenosis (P=ns). Epicardial coronary arterial Doppler represents a valuable tool to detect coronary arterial flow velocity in basal condition. Although changes in flow velocity are easily recorded after coronary occlusion and reperfusion, modifications after partial coronary stenosis are not clearly defined.     

Ischemic preconditioning reduces neutrophil accumulation and myocardial apoptosis

Background. This study tested the hypothesis that ischemic preconditioning (IP) inhibits myocardial apoptosis after a short period of ischemia and reperfusion.

Methods. In 9 anesthetized dogs, the left anterior descending (LAD) coronary artery was occluded for 30 min and reperfused for 3 h (control), while in 9 others, LAD occlusion was preceded by 5 min of occlusion and 5 min of reperfusion (IP). DNA from frozen myocardial tissue samples was extracted, and apoptosis were identified as “ladders” by agarose gel electrophoresis or confirmed histologically using the terminal transferase UTP nick end-labeling (TUNEL) assay. Neutrophil accumulation was detected by measuring cardiac myeloperoxidase activity.

Results. Thirty minutes of LAD occlusion caused a significant decrease in blood flow (colored microspheres), which was comparable between groups. In the control group, DNA ladders occurred in the area at risk (AAR) in six out nine experiments. In contrast, DNA laddering in the AAR was not observed in any of the IP group. AAR in the control group showed a greater percentage of apoptotic cells than IP (6.7 ± 0.9% vs 1.2 ± 0.2%; p < 0.01). Cardiac myeloperoxidase activity (U/g tissue) was significantly reduced from 0.07 ± 0.004 in control to 0.04 ± 0.01 in IP group (p < 0.05).

Conclusions. We conclude that ischemic preconditioning attenuates apoptosis and neutrophil accumulation in the AAR in a model of nonlethal acute ischemia and reperfusion.     

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.     

Ischaemic preconditioning causes increased myocardial vascular resistance but no myocardial contractility changes in pigs after OPCAB

The coronary vascular resistance (CVR) after off pump coronary bypass (OPCAB) surgery has never been clarified and ways of preventing stunning are wanted. We wished to investigate the effect of ischaemic preconditioning (IPC) on the CVR and stunning in the postoperative period after OPCAB. In 20 pigs (80 kg), 7 piezo-electric crystals were placed on the left ventricle to assess global and local myocardial contractility. Coronary vascular resistance was measured as the relation between perfusion pressure and coronary artery blood flow. IPC was obtained in ten pigs with one period of 10 min of coronary occlusion, followed by 15 min of reperfusion and 20 min of ischaemia. Ten control animals were exposed to 20 min of ischaemia only. Reperfusion was allowed for 120 min. The CVR was higher in the IPC group (measured by the slopes of the curves in the reperfusion period) (IPC: -0.33 (CI: (-0.62)-(-0.03)); Control: 0.31 (CI: (-0.03)-(0.67)), P<0.005. There was no difference in the local myocardial contractility (slopes of the curves in the reperfusion period) (IPC: -0.004+/-0.01; Control: -0.005+/-0.01). In conclusion, there was no alteration in myocardial contractility, but increased CVR in the early reperfusion period in animals preconditioned before sustained ischaemia.     

Sodium-hydrogen exchange inhibition attenuates in vivo porcine myocardial stunning

BACKGROUND: Inhibition of the sodium-hydrogen exchanger isoform 1 with HOE-642 (cariporide) has been shown to protect against ischemia-reperfusion injury and to decrease myocardial cell death in numerous animal preparations; however the effects of cariporide in stunned myocardium are not as well understood. We sought to determine whether cariporide attenuated myocardial stunning in vivo. METHODS: Open chest anesthetized pigs (22-33 kg) were subjected to 15 min of left anterior descending coronary artery (LAD) occlusion followed by 3 h of reperfusion. Regional ventricular function was assessed by segment shortening. Contractility was measured by stroke work and by load-insensitive preload recruitable stroke work and preload recruitable stroke work area. Vehicle or HOE-642 (1 mg/kg, IV) was administered 10 min before LAD occlusion. RESULTS: Cariporide treatment significantly improved postischemic segment shortening, stroke work, preload recruitable stroke work, and preload recruitable stroke work area and had no systemic hemodynamic effects. After 3 h of reperfusion, control animals recovered 33% +/- 4% and 33% +/- 3% of preischemic LAD segment shortening and preload recruitable stroke work area values, respectively, whereas animals treated with HOE-642 recovered 59% +/- 6% and 57% +/- 6%, respectively (p < 0.05). Seven (39%) of 17 control animals exhibited ventricular fibrillation during reperfusion; none of the cariporide-treated pigs fibrillated. CONCLUSIONS: Sodium-hydrogen exchange inhibition can attenuate postischemic myocardial stunning in addition to its well-described anti-infarct properties. Inhibition of the sodium-hydrogen exchanger may be beneficial in patients susceptible to postischemic myocardial dysfunction associated with cardiac surgery.     

Beneficial effects of ischemic preconditioning on right ventricular function after coronary artery bypass grafting

BACKGROUND: Preservation of right ventricular myocardium is unsatisfactory in patients with critical stenosis or occlusion of the right coronary artery. The aim of this study was to investigate whether ischemic preconditioning (IP) improved the recovery of right ventricular function after coronary artery bypass grafting. METHODS: Forty patients with three-vessel disease who had coronary artery bypass grafting were randomly assigned to the IP group (n = 20) or control group (n = 20). In the IP group, two cycles of two minutes of ischemia after three minutes of reperfusion were given before cross-clamping. Hemodynamic data were collected. Right ventricular ejection fraction was measured by thermodilution. RESULTS: Right ventricular ejection fraction and right ventricular systolic volume index were decreased post-operatively (lowest value at 6 hours postoperatively). The changes in right ventricular ejection fraction were significantly milder in the IP group postoperatively (p = 0.012). The decrease in right ventricular systolic volume index postoperatively was also less in IP patients (p = 0.002). Fewer inotropic drugs were used in the IP group compared with controls. CONCLUSIONS: Ischemic preconditioning had a myocardial protective effect on recovery of right ventricular contractility in patients who had coronary artery bypass grafting.     

Haemodynamic and EKG changes in patients undergoing minimally invasive direct coronary artery bypass

BACKGROUND AND OBJECTIVES: The objective of the report is to monitor, in patients undergoing minimally invasive direct coronary artery bypass surgery (MIDCAB), the haemodynamic parameters, ST segment changes and the incidence of arrhythmias during clamping of the coronary artery and following reperfusion. METHODS: Twelve patients scheduled for elective MIDCAB surgery during isoflurane anesthesia were enrolled in the study. Patients were monitored by a pulmonary artery thermodilution catheter, an arterial line and 5 leads ECG. The different haemodynamic parameters, the ST segment changes, as well as the occurrence of arrhythmias during coronary clamping and ten minutes following reperfusion were compared to the control values. RESULTS: No significant changes in the cardiac index followed clamping of the coronary artery. However, the ST segment was significantly elevated. Following coronary reperfusion, the ST segment recovered to the baseline values, and the cardiac index significantly increased more than the baseline value (3.5 +/- 1.1 l/min/m2 vs 2.6 +/- 0.7 l/min/m2). However, reperfusion was associated with multiple ventricular extrasystoles in four patients. The elevation of the ST segments during coronary clamping was higher in the four patients who developed reperfusion arrhythmias (0.9 +/- 0.4 mm); one of the patients had preoperative frequent VPBs, two patients had history of unstable angina, while the fourth patient had 70% proximal stenosis of the LAD and recent myocardial infarction. CONCLUSIONS: Coronary occlusion in patients undergoing MIDCAB can result in ST segment elevation, followed by reperfusion ventricular extrasystoles. The reperfusion arrhythmias were observed in patients showing a significant elevation of the ST segment during coronary occlusion; risk factors included a preoperative history of arrhythmia, unstable angina, recent MI, and/or 70% LAD stenosis. The rapid restoration of the control ST segment level and the significant increase of cardiac output following coronary reperfusion suggest that isoflurane anesthesia may have provided a degree of myocardial protection during coronary clamping and reperfusion.     

Acute brain death abolishes the cardioprotective effects of ischemic preconditioning in the rabbit

BACKGROUND: Myocardial preconditioning with brief coronary artery occlusions before a sustained ischemic period is reported to reduce infarct size. We wished to evaluate whether ischemic preconditioning (IP) is efficient in an experimental brain death (BD) model in the rabbit. METHODS: Rabbits were randomized into four experimental groups of eight animals each. In the control group (CTRL), anaesthetized rabbits were subjected to 30 min of left coronary marginal branch occlusion and 90 min of reperfusion without any pretreatment. In the CTRL+IP group, anaesthetized rabbits were preconditioned with a 3-min ischemia and 3-min reperfusion sequence before coronary occlusion. In the BD group, rabbits were subjected to 90 min of BD before 30 min of coronary occlusion and 90 min of reperfusion. In the BD+IP group, BD rabbits were preconditioned as in the CTRL+IP group before coronary occlusion. BD was induced by rapid inflation of an intracranial balloon and was validated by clinical and electroencephalographic examinations. At the termination of the experiment, left ventricular volume (LVV), myocardial volume at risk (VAR) and infarct volume (IV) were determined with methylene blue and tetrazolium staining and were measured using planimetry. RESULTS: LW was not significantly different among the four experimental groups (CTRL, 6.54+/-0.90 cm3; CTRL+IP, 5.92+/-0.60 cm3; BD, 5.87+/-0.81 cm3; BD+IP, 6.16+/-0.95 cm3; P=ns). Furthermore, myocardial VAR, expressed as a percentage of LVV, was not significantly different between groups (CTRL, 20.0+/-4.2%; CTRL+IP, 22.32+/-2.25%; BD, 21.38+/-3.36%; BD+IP, 21.64+/-3.39%; P=NS). IV, expressed as a percentage of VAR, was significantly reduced in the CTRL+IP group compared with the CTRL group (15.76+/-8.47% vs. 49.95+/-1.51%; P<0.0001). In contrast, there was no significant difference in IV, expressed as a percentage of VAR, between the BD and the BD+IP groups (50.0+/-1.52% vs. 49.72+/-1.58%; P=NS). CONCLUSION: The data indicate that the infarct-limiting effect of IP is lost in BD rabbits. Thus, the clinical potential of IP in the context of organ transplantation seems to be severely compromised.     

Thoracic epidural anesthesia reduces myocardial infarct size after coronary artery occlusion in dogs

The effect of thoracic epidural anesthesia (TEA) with lidocaine on regional myocardial blood flow (RMBF), hemodynamic performance, and myocardial infarct size after coronary artery occlusion was assessed in 21 dogs. In seven dogs, the left anterior descending coronary artery (LAD) was temporarily occluded twice: once before TEA (control) and once during TEA. Systemic hemodynamic parameters, RMBF (using radionuclide-labeled microspheres), and epicardial electrocardiographic maps (15 sites) were obtained before and 15 min after each temporary LAD occlusion. Compared with the ischemic period before TEA, the following were decreased during ischemia with TEA: heart rate, ST segment elevation, cardiac index, the peak first time derivative of left ventricular (LV) pressure, LV tension-time index, the rate-pressure product, and LV stroke-work index. Ischemic zone endocardial RMBF was increased from a control value of 26 +/- 6% to 36 +/- 6% of normal during TEA (P less than 0.05). An additional 14 dogs randomly received either TEA (1% lidocaine, 10 ml/hr) or epidural saline plus 1% lidocaine (10 ml/hr, intramuscularly), beginning 1 hr after LAD occlusion. After 6 hr, the heart was removed and the left ventricle was sectioned parallel to the atrioventricular groove. The infarcts (tetrazolium-stained) were 46% smaller with TEA than with saline, 15.4 +/- 1.8% vs 28.7 +/- 2.3% of the left ventricle (P less than 0.05). Thus TEA reduced hemodynamic correlates of myocardial O2 consumption, improved regional (ischemic zone) endocardial perfusion, and reduced the extent of myocardial infarction.     

Lidocaine enhances intraoperative ventricular defibrillation

The efficacy of lidocaine during myocardial reperfusion in coronary artery bypass surgery was evaluated in 20 patients randomly assigned to a control group (n = 10) or to receive lidocaine, 1 mg/kg intravenously 5 min before aortic unclamping and cardiac reperfusion, followed by infusion at 40 micrograms X kg-1 X min-1 (n = 10). We recorded ECG leads II and V5 continuously, and number, energy, and current of direct current (DC) shocks starting at 1 joule. The number of low energy DC shocks to sustained defibrillation (5.5 +/- 2.0 vs 3.5 +/- 2.0, mean +/- SD, P less than 0.05) decreased significantly with lidocaine infusion. The energy (11.0 +/- 6.3 vs 5.6 +/- 3.9 joules, P less than 0.05) and current (12.7 +/- 4.2 vs 8.9 +/- 4.7 amperes, not significant) likewise decreased with lidocaine infusion. Energy and current for the first successful shock, although lower in the lidocaine group, were not statistically significantly lower than in the control group. Initial reperfusion rhythm was not influenced by lidocaine. Plasma electrolyte levels, arterial blood gas tensions, myocardial temperature, and surgical technique--factors known to influence defibrillation--were similar in all patients. Administration of lidocaine during myocardial reperfusion allows defibrillation with fewer DC shocks of lower energy and current.     

Continuous versus intermittent cardioplegia in the presence of a coronary occlusion

Coronary artery occlusions can alter the distribution of cardioplegia and result in ischemic damage. This study was undertaken to determine whether continuous antegrade cardioplegia delivery would result in colder temperatures and provide better washout of acid metabolites than is possible with intermittent antegrade cardioplegia when coronary occlusions are present. Twenty pigs were placed on cardiopulmonary bypass and underwent 2 hours of ischemic arrest with occlusion of the middle left anterior descending coronary artery followed by 1 hour of reperfusion without occlusion of that artery. Ten pigs received intermittent (every 20 minutes) antegrade potassium crystalloid cardioplegia (4 degrees C), and 10 others had the same solution given continuously (30 mL/min). Cardioplegia distribution was assessed by continuous monitoring of myocardial pH (Khuri pH probe) and temperature in the region beyond the occlusion of the left anterior descending coronary artery. Both cardioplegic techniques resulted in tissue acidosis (continuous group, 6.69 +/- 0.08, versus intermittent group, 6.73 +/- 0.07; not significant). Average temperature in the left anterior descending coronary artery during arrest was also similar in both groups (continuous group, 18.3 degrees +/- 0.5 degrees C, versus intermittent group, 18.2 degrees +/- 0.5 degrees C). Because of these metabolic changes, both cardioplegic techniques resulted in abnormal wall motion in the anteroseptal region using two-dimensional echocardiography, but the scores were not significantly different (continuous group, 1.5 +/- 0.3, versus intermittent group, 1.6 +/- 0.4; 4 = normal to 0 = dyskinesia).(ABSTRACT TRUNCATED AT 250 WORDS)     

Off-pump coronary bypass grafting to double vessel disease with the pharmacological assist of esmolol. An experimental study

BACKGROUND: To demonstrate the surgical efficacy and safety of off-pump coronary bypass grafting to double- or triple-vessel disease, we performed off-pump double bypass grafting using a brief local coronary occlusion with the pharmacological assist of esmolol. METHODS: These experiments were conducted in 30 canine hearts with the left internal thoracic artery (ITA) grafted to the circumflex coronary artery (CFX) and the right ITA grafted to the left anterior descending coronary artery (LAD), off pump, using a brief local coronary occlusion through the left minithoracotomy. The coronary anastomosis was performed using a brief local occlusion of the coronary artery. An anastomosis between the left ITA and the CFX was done first, and then the right ITA and the LAD were anastomosed. Thirty animals were divided into 2 groups, group A (n=15) receiving esmolol just before (10 mg/kg on a bolus) and during the coronary artery occlusion (500 microg/kg/min continuously), and group B (n=15) without administrating esmolol as a control. RESULTS: Operative deaths were 4 in group B and all of group A animals survived (p<0.05). All deaths were attributable to ventricular arrhythmias during/after coronary occlusion. Group B animals necessitating longer coronary occlusion time (more than 15 min) were more likely to fibrillate and more difficult to resuscitate than group A animals requiring coronary occlusion time more than 15 min. Segmental shortening on the echocardiogram demonstrated no significant difference between group A and B in both anterior and posterior wall segment. However, echocardiogram in animals necessitating coronary occlusion time more than 15 min demonstrated that segmental shortening in group A were better than in group B (18 vs 11%, p<0.05), and comparatively greater but not significant in the posterior wall (19 vs 14%). CONCLUSIONS: The use of esmolol may be recommended to off-pump coronary bypass even to the double-vessel bypass, in order to make off-pump approach safer.