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.     

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.     

Myocardial protective effect of lidocaine during experimental off-pump coronary artery bypass grafting.

Off-pump coronary artery bypass grafting (OPCABG) has recently gained popularity. During OPCABG, patients remain vulnerable to ischemic-reperfusion injury due to a temporary coronary occlusion without any active cardioprotection. Some strategies such as ischemic preconditioning (IP) and an intracoronary shunt have been applied with a view to minimizing the effects of ischemia, but the effects of these strategies remain controversial. This study was carried out to investigate the protective effect of lidocaine against myocardial ischemic-reperfusion injury. Twenty-one pigs were assigned to three groups, each consisting of seven pigs. In the control group, using a left internal thoracic artery (LITA) bypass circuit, the left anterior descending coronary artery (LAD) was occluded for 45 min followed by two hours of reperfusion. In the IP group, five min of occlusion followed by 15 min of reperfusion was performed. In the lidocaine group, 2 mg/kg of lidocaine was administered directly into the LAD just before the LAD occlusion. Infarct size expressed as a percentage of the area at risk was significantly smaller in the lidocaine group (2.7+/-4.2%) than in the control group (79.9+/-6.0%, p<0.001) or the IP group (57.0+/-25.9%, p<0.001). Lidocaine exhibited a potent myocardial protective effect in the present OPCABG model.     

An evaluation of a new two-electrode myocardial electrical impedance monitor for detecting myocardial ischemia

The objective of this study was to determine the efficacy of a two-electrode myocardial electrical impedance (MEI) monitor in reproducibly detecting induced myocardial ischemia by comparing MEI changes with hemodynamic changes, including sonomicrometric changes. With institutional approval, 80 dogs were anesthetized with sodium thiamylal, intubated, ventilated, and had venous, arterial, and pulmonary artery catheters placed. Medial sternotomy was performed to facilitate myocardial exposure and allow the left anterior descending coronary artery (LAD) to be isolated. Two pacing electrodes were attached to the myocardium to measure MEI with a monitor. Seventy dogs were randomly assigned to the 15, 30, 45, 60, or 120 min LAD occlusion group. Sonomicrometric transducers were attached to the myocardium of the ten remaining dogs and their LAD was occluded for 36 min. MEI increased immediately after LAD occlusion to a level significantly more (P < 0.05) than baseline and returned to the baseline level upon reperfusion. Twenty dogs developed ventricular fibrillation with no attempts at resuscitation. MEI changes paralleled the sonomicrometric changes expected with ischemia. No significant cardiovascular hemodynamic changes were found with less than 45 min of LAD occlusion. Sixty and 120 min LAD occlusion resulted in significant decreases in cardiac output. The results of these experiments demonstrate that the two-electrode MEI monitor reproducibly changes in response to myocardial ischemia.     

Flow in coronary artery bypass grafts to totally and partially occluded left anterior descending coronary arteries

Flow was determined by electromagnetic flowmeter in vein bypass grafts in 20 patients with a totally occluded left anterior descending (LAD) coronary artery and on 61 patients with a partially occluded LAD. The median flow in LAD grafts was 14.5 ml/min with total LAD occlusion, and 40 ml/min with partial LAD occlusion (p less than 0.001). In cases of total LAD occlusion, the presence of mild or moderate anteroseptal wall dysfunction was associated with more satisfactory flow than was the case with severe anteroseptal wall dysfunction (p less than 0.02). Flows over 25 ml/min were found only when the LAD distal to total occlusion was 1.5 mm or greater. Unsatisfactory flows were consistently found with total LAD occlusion, poor ventricular function, and a distal LAD less than 1.5 mm. Repeat catheterizations to determine an unsatisfactory patency rate under these conditions would be necessary to alter our policy of grafting all suitable vessels beyond a total occlusion.     

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.     

The Effect of Acute Coronary Artery Occlusion during Cardioplegic Arrest and Reperfusion on Myocardial Preservation

A study was undertaken to evaluate the effect of acute occlusion of a coronary artery during cardioplegic arrest on myocardial preservation and to elucidate the influence of reestablishment of flow versus continued occlusion during the phase of myocardial reperfusion. Coronary occlusion was simulated, and myocardial viability was determined by measuring tissue levels of adenosine triphosphate (ATP) and creatine phosphate (CP) in biopsies of the posterior left ventricular wall. Eighteen pigs were divided into three equal groups consisting of animals with (1) patent right coronary arteries during arrest and reperfusion, (2) occluded right coronary arteries during arrest and patent during reperfusion, and (3) occluded right coronary arteries during arrest and reperfusion.The results of ATP and CP measurements showed that while poorer protection was afforded during two-hour arrest when the coronary artery was occluded, the risk of damage was much greater during reperfusion. Failure to restore adequate blood flow by retention of occlusion caused a concurrent decrease in ATP and CP levels below prescribed limits of myocardial tolerance. When occlusion occurs in the clinical setting, impeding cardioplegia and reperfusion, the importance of revascularization is emphasized.     

Acute effects of tourniquet occlusion and intraluminal shunts in beating heart surgery.

OBJECTIVE: MIDCAB and OPCAB revascularization is currently performed with temporary tourniquet occlusion of the coronary artery to achieve a bloodless surgical field. However, a trauma of the vessel wall due to snaring sometimes occurs. The use of temporary intraluminal shunts (TILS) have recently been advocated as an alternative. The aim of this experimental study was to evaluate the acute ultrastructural effects of TILS versus tourniquet occlusion on the coronary vessel wall. METHODS: Twelve pigs (40+/-3 kg) were investigated. In group A (n=6) the left anterior descending (LAD) artery was temporarily occluded with a tourniquet over 20 min. In group B (n=6) a commercially available silicone TILS (1.5-mm diameter, 12-mm length, AnastaFlo, Research Medical Inc.) was placed in the LAD. After 20 min perfusion the TILS was removed and the insertion was repaired. After 30 min reperfusion all animals were killed. Three LAD territories of each animal were examined histopathologically by scanning electron microscopy (SEM), light microscopy (LM) and transmission electron microscopy (TEM). Areas of occlusion or placement of the TILS olives were investigated. RESULTS: SEM revealed ultrastructural alterations in both groups. While marked intimal rupture appeared in all animals of group A, only two of the six animals of group B exhibited superficial endothelial abrasions. LM showed differences of intimal thickness in all groups while TEM revealed severe edema of subendothelial tissue in four of six animals in group A. CONCLUSION: The intimal lesions observed after tourniquet occlusion in our experimental off-pump surgery model confirmed other recent studies. In contrast, utilization of TILS caused only minor damage of the vessel wall. The endothelial abrasions detected in this group may be a consequence of micro-dislocations or insertion maneuvers. Chronic studies are necessary to verify as to whether the mild injury after TILS insertion will result in a reduction or even absence of de-novo stenoses compared with tourniquet occlusion.     

Inotropic response of the salvaged myocardium after acute coronary occlusion

We determined the response of the reperfused myocardium to inotropic stimulation with dobutamine hydrochloride. The middle part of the left anterior descending coronary artery (LAD) was occluded in 15 greyhounds for 3 hours. Group 1 (N = 8) was reperfused for 3 hours in the beating, working heart. Group 2 (N = 7) was put on cardiopulmonary bypass (CPB) for 1 hour, received 500 ml of potassium cardioplegia in the aortic root and in the area of ischemia through an internal mammary-LAD graft, and the LAD was reperfused off CPB for 3 hours. After 3 hours of reperfusion, dobutamine was given at 10 micrograms/kg/min for 20 minutes. Regional myocardial function was determined with subendocardial ultrasonic crystals in the area of ischemia and in the base of the heart; segmental contractility was determined from the ratio of peak left ventricular pressure to end-systolic segment length; and global contractility was determined by the slope of the ventricular pressure wave at a developed pressure of 40 mm Hg. Measurements were made prior to LAD occlusion (control), at the end of 3 hours of reperfusion (6 hours from the beginning of occlusion), and after 20 minutes of dobutamine infusion. Dobutamine infusion improved segmental function in all animals compared with 3 hours of reperfusion. The study shows that the reperfused myocardium responds favorably to inotropic stimulation after 3 hours of occlusion and 3 hours of reperfusion, and that the contractile response both to reperfusion and to inotropic stimulation is greatly affected by the method of reperfusion.     

Antifibrillatory effects of volatile anesthetics in acute occlusion/reperfusion arrhythmias

Halothane, enflurane, and isoflurane were evaluated for antifibrillatory efficacy and compared with lidocaine, propranolol, procainamide, and verapamil in a canine acute left anterior descending (LAD) coronary artery occlusion/reperfusion model with basal pentobarbital anesthesia. Of the antiarrhythmic drugs, only verapamil prevented ventricular fibrillation during occlusion and reperfusion. Halothane 1% inspired after 15 min showed similar protection. Enflurane 2.5% inspired after 15 min resulted in significant protection but caused hypotension after occlusion in 4 of 17 dogs. Isoflurane 1.7% inspired after 15 min showed intermediate results. At inspired concentrations of 0.5% and 1.25%, respectively, halothane and enflurane protected against ventricular fibrillation without hypotension. It is concluded that the volatile anesthetics have antifibrillatory effects in this canine model but differ in their ability to cause hypotension in the presence of proximal LAD coronary artery occlusion.     

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.     

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.     

Intracoronary shunt prevents left ventricular function impairment during beating heart coronary revascularization.

OBJECTIVE: Beating heart coronary revascularization is becoming increasingly popular world-wide. Temporary occlusion of the coronary artery is often required in order to perform the anastomosis. An alternative method to maintain perfusion is to use an intracoronary shunt. In this study, we monitored global left ventricular function and regional wall motion in the presence or absence of a shunt using transesophageal echocardiography (TEE). METHOD: Left ventricular wall motion score index (WMSI), wall motion score (WMS) in the left anterior descending (LAD) coronary artery territory, and ejection fraction (EF%) were measured by multiplane TEE during construction of the left internal mammary artery (LIMA)-LAD coronary artery anastomosis in 40 patients undergoing revascularization with or without the use of a shunt. WMSI was assessed preoperatively, 1, 3 and 6 min during the construction of the anastomosis and after 5 min of reperfusion. WMS was assessed at 6 min during anastomosis and after 5 min of reperfusion. EF% was calculated preoperatively, 5 min into the construction of the anastomosis, and 5 min after reperfusion. RESULTS: During construction of the anastomosis, when the shunt was used, there were no changes in WMSI, WMS in the LAD territory or EF%. A significant decline in these parameters was seen in the group in which the shunt was not used, although on reperfusion all the values returned to baseline control. CONCLUSION: (i) occlusion of the LAD to perform the anastomosis results in temporary impairment in left ventricular function with complete recovery on reperfusion; (ii) the use of an intracoronary shunt presumably by maintaining myocardial perfusion prevents deterioration in ventricular function; (iii) from this data it seems therefore advisable to use an intracoronary shunt in patients with unstable angina, poor left ventricular function, or in cases in which a longer time to perform the anastomosis is anticipated.     

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.     

Effects of liraglutide and ischemic postconditioning on myocardial salvage after I/R injury in pigs*

Objectives. Acute STEMI is routinely treated by acute PCI. This treatment may itself damage the tissue (reperfusion injury). Conditioning with GLP-1 analogs has been shown to reduce reperfusion injury. Likewise, ischemic postconditioning provides cardioprotection following STEMI. We tested if combined conditioning with the GLP-1 analog liraglutide and ischemic postconditioning offered additive cardioprotective effect after reperfusion of 45?min coronary occlusion of left anterior descending artery (LAD). Design. Fifty-eight non-diabetic female Danish Landrace pigs (60?±?10kg) were randomly assigned to four groups. Myocardial infarction (MI) was induced by occluding the LAD for 45?min. Group 1 (n?=?14) was treated with i.v. liraglutide after 15?min of ischemia. Group 2 (n?=?17) received liraglutide treatment concomitant with ischemic postconditioning, after 45?min of ischemia. Group 3 (n?=?15) recieved ischemic postconditioning and group 4 (n?=?12) was kept as controls. Results. No intergroup differences in relative infarct size were detected (overall mean 57?±?3%; p?=?0.68). Overall mortality was 34% (CI 25–41%) including 26% post-intervention, with no intergroup differences (p?=?0.99). Occurrence of ventricular fibrillation (VF) was 59% (CI 25–80%) including 39% postintervention with no intergroup differences (p?=?0.65). Conclusions. In our closed-chest pig-model, we were unable to detect any cardioprotective effect of liraglutide or ischemic postconditioning either alone or combined.     

Myocardial glycerol release, arrhythmias and hemodynamic instability during regional ischemia-reperfusion in an open chest pig model

BACKGROUND: To develop cardioprotection against peri-operative myocardial ischemia-reperfusion injury, we need animal models where the local metabolism and blood flow are studied concomitantly with the global circulatory consequences during regional coronary occlusion. METHODS: In six anesthetized domestic pigs, the largest branch of the circumflex artery was occluded for 30 min. Microdialysate was sampled from the ischemic and non-ischemic myocardium along with continuous measurements of local coronary artery flow, global hemodynamics and registration of arrhythmias, from baseline through to 30 min of ischemia and 180 min of reperfusion. RESULTS: During ischemia, the microdialysate glucose concentration decreased, the glycerol concentration increased and the lactate/pyruvate ratio increased significantly. For glycerol, there was a further increase at reperfusion. During ischemia, cardiac output was unchanged; however, during reperfusion there was a significant drop lasting for several minutes, longer than the period in which an increased number of arrhythmias were registered. CONCLUSION: The present study demonstrates deranged circulation and arrhythmias corresponding to ischemic metabolism after regional myocardial ischemia and reperfusion. Reperfusion induced more pronounced circulatory changes than the actual ischemia. A substantial increase in myocardial glycerol release seems to be a marker of ischemic metabolism and may prove to be an indicator of reperfusion injury.     

Internal thoracic artery flow competition: studies in a canine H-graft model.

OBJECTIVE: Internal thoracic artery (ITA) flow competition is a diversion of graft flow through intact ITA branches with a net decrease in perfusion to the grafted coronary. Although a widely acknowledged phenomenon, the conditions under which flow competition occurs have not been established. This is examined in a canine H-graft model. METHODS: Eight dogs had a right ITA segment interposed (H-graft) between their in situ left ITA (LITA) and the snared left anterior descending (LAD) coronary artery. Proximal LITA and H-graft flows were measured at baseline and during pacing-induced tachycardia, phenylephrine-induced hypertension, and nitroprusside-induced hypotension. Flows were measured with the distal LITA open and occluded. Two additional animals were subjected to eight separate 2-min periods of LAD ischemia, after which post-ischemic H-graft flow measurements were obtained with and without distal LIMA occlusion. RESULTS: During baseline conditions, proximal LITA flow was greater when the distal LITA was open rather than occluded (46+/-15 versus 35+/-12 ml/min, respectively; P=0.002), but H-graft flow did not change significantly (32+/-18 versus 35+/-18 ml/min, respectively; P=0.21). Similarly, occlusion of the distal LITA had no impact on H-graft flow during tachycardia, hypertension, or hypotension. Only in animals subjected to transient LAD ischemia did H-graft flow increase with distal LITA occlusion, albeit marginally (65+/-7-70+/-9 ml/min, occluded versus open, respectively; P=0.04). CONCLUSIONS: Mild diversion of flow from the LAD was demonstrated during immediate post-ischemic coronary reperfusion only, and could not be elicited under any other physiologic condition. These data suggest that flow competition is unlikely to constitute a clinically significant limitation to the use of H-grafts or other modalities that leave ITA branches patent.     

局部心肌顿抑对全身血液动力学及心肌氧供需平衡的影响

目的 观察局部心肌顿抑对全身血液动力学及心肌氧供需平衡的影响。方法 杂种犬３３条,常温下冠状动脉左前降支根部阻断１５ｍｉｎ,观察再灌注后全身血液动力学、冠脉流量及缺血心肌氧供氧耗的变化。结果 ＭＡＰ在冠脉阻断期间稍下降,再灌注后升至基础水平;ＨＲ在缺血／再灌注过程中均明显增快;冠脉阻断后,ＣＯ、ＳＶ、左室收缩功指数均迅疾下降,再灌注５ｍｉｎ略有升高,之后进行性下降;再灌注后,体循环血管阻力、肺血管     

Selective retrograde venous revascularization of the myocardium when PCI or CABG is impossible: investigation in a porcine model

We investigated the possibility of nourishing the myocardium through selective retrograde coronary venous bypass grafting (CVBG) with an off-pump technique and evaluated various methods of monitoring the physiological effects of this procedure. In a porcine model, the left internal mammary artery (LIMA) was anastomosed to the left anterior descending coronary vein (LAD vein) in an off-pump procedure. The LAD vein was ligated proximal to the anastomosis. The LAD artery was ligated proximally. The physiological effects were monitored using microdialysis, tissue oxygen tension, blood flow in LIMA, blood samples, and hemodynamic and histological analyses. As controls, 5 pigs underwent surgery involving only LAD artery ligation without CVBG. CVBG with LAD ligation was performed in 16 pigs; 12 survived CVBG and were monitored for 2-2.5 hours while in sinus rhythm, a 75% salvage rate after an otherwise lethal LAD artery occlusion. Immediately after LAD artery ligation, the anterior wall of the left ventricle became cyanotic and hypokinetic. Over time it regained color and contractility as flow in the LIMA increased. Microdialysis showed a significant increase in lactate. Initially tissue oxygen tension decreased, but with time some recovery was seen. Cardiac troponin T was elevated. Histological analysis showed ischemic changes. In control pigs, microdialysis was performed for 1.5 hours up to LAD artery ligation, after which all pigs died in ventricular fibrillation arrest. No increase in lactate was observed. These results indicate that after LAD artery occlusion, CVBG can nourish the myocardium to a certain extent and prevent death in the majority of cases, although varying degrees of ischemia remain.     

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.