Effect of coronary artery occlusion on myocardial protection by retroperfusion of cardioplegic solutions

Coronary artery stenoses impede delivery of cardioplegic solutions infused through the aortic root. Therefore, the efficacy of retroperfusion of cardioplegic solution through the coronary sinus was assessed in dogs subjected to cold, potassium cardioplegic arrest. Group I (N = 15) had the left anterior descending (LAD) coronary artery occluded throughout ischemia while Group II (N = 15) had a patent LAD. Transmural biopsies of both the left ventricular (LV) apex and right ventricle (RV) were assayed for adenosine triphosphate (ATP) and creatine phosphate (CP). Regional wall temperatures were sequentially monitored. The time from aortic cross-clamping to electrical arrest varied widely, but the mean arrest time of each group was similar (174 +/- 22 vs 175 +/- 28 sec). (table; see text) Comparable depletion of ATP stores (vs preischemia) occurred in each ventricle regardless of coronary artery patency. Similarly, CP stores were depleted 60-72% (P less than 0.01) during ischemia. Mean temperatures during arrest of the RV and LV (17.2-19.5 degrees C) did not differ and were not affected by LAD occlusion. Coronary venous resistance remained constant with repetitive infusions. These data suggest that myocardial protection with coronary sinus retroperfusion is independent of arterial patency, but is suboptimal, perhaps due to the prolonged time needed to induce ventricular arrest.     

Effects of initial reperfusion temperature and pressure after prolonged cardioplegic ischemic arrest. A metabolic and functional study in rat hearts

The effects of temperature and pressure during early cardiac reperfusion after 3.5 hours of hypothermic, cardioplegic ischemia were investigated in isolated Langendorff-perfused rat hearts. The hearts were randomized in two groups and subjected to different techniques of reperfusion. The group I hearts were exposed to rapidly rising perfusion pressure and temperature, and in group II slowly rising pressure and temperature were employed. After 60 min of reperfusion, left ventricular developed pressure, coronary flow and tissue content of high-energy phosphates were evaluated. Left ventricular pressure and coronary flow were significantly better preserved in group II. Recovery of adenosine triphosphate and creatine phosphate was significantly lower in group I (5.27 +/- 0.38 and 8.72 +/- 0.62 mumol x g dry weight-1) than in group II (9.31 +/- 0.41 and 14.97 +/- 0.62). The study thus demonstrated that functional recovery, restoration of coronary flow and normalization of high-energy phosphate stores after long periods of hypothermic cardioplegic ischemia can be considerably influenced by the employed reperfusion technique.     

Myocardial protection in coronary occlusion by retrograde cardioplegic perfusion via the coronary sinus in dogs. Preservation of high-energy phosphates and regional function

The lack of adequate myocardial preservation because of maldistribution of cardioplegic solution in coronary artery disease remains a perplexing problem. We compared two methods of cardioplegic delivery in dogs: antegrade aortic root perfusion (Group I) and retrograde coronary sinus perfusion (Group II). Metabolic changes and regional function in the coronary occlusion model, in which the left anterior descending artery was occluded at its prediagonal portion, were studied. In the distribution of the occluded coronary artery, adenosine triphosphate and total adenine nucleotides at the end of 120 minutes of ischemia were preserved better in Group II (16.80 and 22.94 mumol/gm dry weight) than in Group I (11.06 and 16.19 mumol/gm dry weight, p less than 0.05). Lactate accumulation tended to be higher in Group I than in Group II (114.0 and 87.2 mumol/gm dry weight, respectively; not significant). Percent recovery of segmental shortening was also better in Group II than in Group I (100% and 22.3% at the same left atrial pressure, 4 mm Hg; p less than 0.01). In the region supplied by the intact coronary artery, there were no significant differences between the two groups with regard to metabolic changes and regional function. These observations suggest that retrograde cardioplegic perfusion via the coronary sinus is preferable for surgically treatment of severe coronary artery disease.     

Myocardial protection during prolonged aortic cross-clamping. Comparison of blood and crystalloid cardioplegia

We compared the ability of blood and crystalloid cardioplegia to protect the myocardium during prolonged arrest. Twelve dogs underwent 180 minutes of continuous arrest. Group I (six dogs) received 750 ml of blood cardioplegic solution (potassium chloride 30 mEq/L) initially and every 30 minutes. Group II (six dogs) received an identical amount of crystalloid cardioplegic solution (potassium chloride 30 mEq, methylprednisolone 1 gm, and 50% dextrose in water 16 ml/L of electrolyte solution). Temperature was 10 degrees C and pH 8.0 in both groups. Studies of myocardial biochemistry, physiology, and ultrastructure were completed before arrest and 30 minutes after normothermic reperfusion. Biopsy specimens for determination of adenosine triphosphate were obtained before, during, and after the arrest interval. Regional myocardial blood flow, total coronary blood flow, and myocardial oxygen consumption were statistically unchanged in Group I (p greater than 0.05). Total coronary blood flow rose 196% +/- 49% in Group II (p less than 0.005), and left ventricular endocardial/epicardial flow ratio fell significantly in this group from 1.51 +/- 0.18 to 0.8 +/- 0.09, p less than 0.01 (mean +/- standard error of the mean. The rise in myocardial oxygen consumption was not significant in this group (34% +/- 36%, p greater than 0.05). Ventricular function and compliance were statistically unchanged in both groups. In Group II, adenosine triphosphate fell 18% +/- 3.4% (p less than 0.005) after 30 minutes of reperfusion; it was unchanged in Group I. Ultrastructural appearance in both groups correlated with these changes. We conclude that blood cardioplegia offers several distinct advantages over crystalloid cardioplegia during prolonged arrest.     

Chronic Hypoxemia Depresses Global Ventricular Function and Predisposes to the Depletion of High-Energy Phosphates during Cardioplegic Arrest: Implications for Surgical Repair of Cyanotic Congenital Heart Defects

Persistence of impaired ventricular function after repair of cyanotic congenital heart defects may be due to previous exposure to chronic hypoxemia or to perioperative ischemic injury. Clarification of this phenomenon was sought in a canine model of cyanotic cardiovascular disease (Group I), in which the left atrium was anastomosed proximal to the banded pulmonary artery. Animals that had pulmonary artery banding alone (Group II) or no prior surgical intervention (Group III) served as controls. All Group I animals became cyanotic during the study period (arterial oxygen tension, 38 ± 4 mm Hg; hematocrit, 55 ± 5%). Radionuclide-determined ejection fractions performed three months after operation showed significant depression of global biventricular function by 16 to 29% (p < 0.05) compared with groups II and III. On cardiopulmonary bypass, all hearts were subjected to 4°C potassium cardioplegic arrest and reperfusion with serial assays for myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) levels. The ATP and CP stores in each ventricle were similar at all sampling intervals, and preischemic levels were comparable in cyanotic and control groups. However, ATP levels were significantly depressed 37 to 43% from preischemic levels (p < 0.02) after arrest and reperfusion in cyanotic dogs, but they were preserved in Groups II and III. During ischemia, CP stores were depleted to 27% of preischemic values in Group I but only to 46 to 63% of preischemic levels in the control groups (p < 0.05). These data indicate that chronic hypoxemia impairs global ventricular function and predisposes to the accelerated depletion of high-energy phosphates during cardioplegic arrest. The formulation of new intracoronary perfusates for the cyanotic myocardium seems warranted.     

Effects of antegrade cardioplegic infusion with simultaneously controlled coronary sinus occlusion on preservation of regionally ischemic myocardium after acute coronary artery occlusion and reperfusion

This study was conducted to assess the protective effects of antegrade infusion of cardioplegic solution with simultaneously controlled coronary sinus occlusion on regionally ischemic myocardium after acute coronary occlusion and reperfusion. Twelve sheep were subjected to 1 hour of occlusion of the distal left anterior descending coronary artery. Sheep in group I (n = 6) were subjected only to infusion of potassium crystalloid cardioplegic solution into the aortic root, whereas in group II (n = 6) a stitch was snared around the proximal coronary sinus for its subsequent occlusion during antegrade infusions of cardioplegic solution. All animals were placed on cardiopulmonary bypass. Five hundred milliliters of cardioplegic solution at 4 degrees to 8 degrees C was administered in three divided doses during the total cross-clamp period of 30 minutes. The occlusion of the left anterior descending artery was then released, and the animals were weaned from bypass and studied for an additional 4 hours. Coronary sinus pressure, myocardial temperature, regional function assessed by pairs of ultrasonic crystals, global function assessed by rate of rise of left ventricular pressure and cardiac output, and the area at risk and area of necrosis were determined. The heart was excised at the end of the experiment and stained. Animals treated by the technique of antegrade infusion combined with coronary sinus occlusion had more homogeneous myocardial cooling during cardioplegic infusions and better recovery of the first derivative of left ventricular pressure and regional segment shortening at 90 and 270 minutes of reperfusion than those treated with antegrade infusion alone (p less than 0.01 and p less than 0.05, respectively). The group treated by antegrade infusion of cardioplegic solution combined with coronary sinus occlusion had an area of necrosis/area at risk ratio of 40.5% +/- 1.2%; the antegrade infusion group, 58.3% +/- 4.1% (p less than 0.01). These data suggest that antegrade infusion combined with coronary sinus occlusion may be an improved method of global and regional myocardial protection in the presence of an occluded coronary artery.     

The effects of retrograde cardioplegia technique on myocardial perfusion and energy metabolism: a magnetic resonance imaging and localized phosphorus 31 spectroscopy study in isolated pig hearts

OBJECTIVE: The present work was designed to study the myocardial perfusion and energy metabolism during retrograde cardioplegia performed with different methods, including deep coronary sinus cardioplegia, coronary sinus orifice cardioplegia, and right atrial cardioplegia. METHODS: Isolated pig hearts were subjected to antegrade cardioplegia, right atrial cardioplegia, deep coronary sinus cardioplegia, and coronary sinus orifice cardioplegia in a random order. Cardioplegic distribution was assessed by T1-weighted magnetic resonance imaging in 1 group of hearts (n = 8). The flow dynamics of cardioplegia were assessed by T2*-weighted imaging in a second group of hearts (n = 8). RESULTS: T1-weighted images revealed an apparent perfusion defect in the posterior wall of the left ventricle, the posterior portion of the interventricular septum, and the right ventricular free wall during deep coronary sinus cardioplegia. The perfusion defect observed in the first 2 regions with deep coronary sinus cardioplegia resolved with coronary sinus orifice cardioplegia. Right atrial cardioplegia provided the most homogeneous perfusion to all regions of the myocardium relative to the other 2 retrograde cardioplegia modalities. T2*-weighted images showed that the 3 retrograde cardioplegia modalities provided similar cardioplegic flow velocities. Localized phosphorus 31 spectroscopy showed that the levels of adenosine triphosphate and phosphocreatine were significantly lower in the posterior wall (adenosine triphosphate, 42.86% +/- 5.91% of its initial value; phosphocreatine, 11.43% +/- 11.3%) than the anterior wall (adenosine triphosphate, 89.19% +/- 8.83%; phosphocreatine, 59.54% +/- 12.58%) of the left ventricle during 70 minutes of normothermic deep coronary sinus cardioplegia. CONCLUSIONS: Deep coronary sinus cardioplegia results in myocardial ischemia in the posterior wall of the left ventricle and the posterior portion of the interventricular septum, as well as in the right ventricular free wall. Coronary sinus orifice cardioplegia improves cardioplegic distribution in these regions. Relative to deep coronary sinus cardioplegia and coronary sinus orifice cardioplegia, right atrial cardioplegia provides the most homogeneous perfusion.     

Inadequate cardioplegic protection with obstructed coronary arteries.

To determine the contribution of complete cardioplegia to the preservation of left ventricular (LV) function, we put ultrasonic transducers in the anterior and posterior walls of the left ventricle in 18 dog hearts. The dogs were subjected to global ischemia for 60 minutes at 28°C, and the speed of segment shortening (dl/dt) and percent of systolic shortening of the two wall regions before and after ischemic manipulations were measured. When cardioplegic perfusion was uniform, there was no significant difference between the anterior and posterior walls in any of the variables measured, and global LV function (stroke work) was well preserved. However, when the left anterior descending coronary artery was occluded during cardioplegic infusion, there was significant dysfunction after reperfusion of the anterior wall: without perfusion, the anterior segments recovered only 41% (5.9/14.3 mm/sec) of preischemic dl/dt, while the perfused anterior segments retained 78% (11.4/14.6 mm/sec) of control dl/dt (p < 0.05). The experimental anterior regions regained only 36% of preischemic systolic shortening, while the anterior segments in the homogeneously perfused hearts were indistinguishable from internal controls (p < 0.01).Regionally inadequate cardioplegic protection during coronary artery bypass graft operation may contribute to perioperative infarction and LV dysfunction, and appropriate timing of anastomoses to ensure early cardioplegic perfusion of all ischemic myocardium is important.     

Cardiac performance during reperfusion improved by pretreatment with oxygen free-radical scavengers

We studied the effects of oxygen free radicals on cardiac performance during reperfusion of ischemic myocardium. The pig heart, isolated in situ, was subjected to 60 minutes of regional ischemia at normothermia by occlusion of the left anterior descending coronary artery followed by 60 minutes of hypothermic cardioplegic arrest and 60 minutes of normothermic reperfusion. The oxygen free-radical scavengers, superoxide dismutase and catalase, were administered before occlusion of the left anterior descending coronary artery in the experimental group. The generation of free radicals in the untreated group, estimated by the measurement of malondialdehyde in the perfusate, was significant during reperfusion and was associated with a corresponding increase in creatine kinase. Superoxide dismutase and catalase significantly slowed the appearance of malondialdehyde and the release of creatine kinase during reperfusion. Superoxide dismutase and catalase did not alter coronary flow and myocardial oxygen extraction or consumption during occlusion of the left anterior descending coronary artery; however, coronary flow and oxygen consumption were significantly higher (p less than 0.05) during reperfusion in hearts treated with antioxidants. Left ventricular developed pressure and its maximum first derivative were measured under isovolumic conditions. In the untreated group, left ventricular developed pressure and its maximum first derivative declined to 61.1% and 57.1% of baseline values, respectively, after 60 minutes' occlusion of the left anterior descending, and to 45% of baseline values after 15 minutes of reperfusion. The decline in left ventricular developed pressure and its maximum first derivative during reperfusion was significantly (p less than 0.05) inhibited by superoxide dismutase and catalase, but left ventricular end-diastolic pressure was not significantly altered. These results implicate oxygen-derived free radicals in the injury resulting from reperfusion of ischemic myocardium and suggest that oxygen free-radical scavengers effectively protect against such injury.     

Blockade of ATP-sensitive K+ channel abolishes the anti-ischemic effects of isoflurane in dog hearts

Background: Although isoflurane is reported to have a protective effect against ischemic damage on the myocardium, the mechanisms of this effect are not clear. Activation of adenosine triphosphate sensitive potassium (KATP) channels is indicated to protect myocardium during ischemia. Thus, it was hypothesized that if isoflurane could activate KATP channels, blockade of KATP channels would decrease its cardioprotective effect.
Methods: Mongrel dogs, anesthetized with morphine, urethane, and chloralose, were subjected to 15 min of left anterior descending coronary artery occlusion followed by 60 min reperfusion. The dogs were divided into three groups: the control group (n=8), IS0 group (n=8) and ISOGC group (n=8). In the IS0 and ISOGC groups, 1 MAC of isoflurane was administrated during ischemia and reperfusion. In the ISOGC group, 0.3 mg/ kg of glibenclamide, the KATP channel blocker, was given 45 min before ischemia. Full-thickness samples of myocardium were obtained and the concentrations of adenosine monophosphate, adenosine diphosphate, adenosine triphosphate (ATP), creatine phosphate and lactate in the endocardial portion of the myocardium were measured.
Results: The ischemia-reperfusion caused a 25.4% and 27.6% reduction of myocardial ATP in the control and ISOGC groups, respectively. In contrast, the IS0 group showed only 11.0% reduction of AT, which was significantly lower compared to the other groups ( P < 0.01).
Conclusions: Our results shows that blockade of the KATP channel abolishes cardioprotective effects of isoflurane in myocardial ischemia-reperfusion. The KATP channel may play a role in the ATP-sparing effect of isoflurane.     

Significance of coronary artery bypass grafting to totally occluded left anterior descending coronary artery

The comparative studies on operative and hemodynamic results following coronary artery bypass grafting (CABG) were performed in 15 patients with totally occluded left anterior descending coronary artery (TOLAD) and 24 with partially occluded LAD (POLAD). There were two operative deaths and one whose graft was obstructed in POLAD. Four patients were revealed to have transmural myocardial infarction (TMI) in the region other than anterior segment on the preoperative electrocardiogram. Following results were obtained in 13 TOLAD (Group I) and 19 POLAD (Group II) with two subgroups, a: without TMI and b: with anterior TMI, whose all bypass grafts were patent. Left ventricular ejection fraction, Mean Vcf and left ventricular anterior, apical segmental wall motion significantly increased postoperatively in all groups, whereas postero-inferior segmental wall motion did not increase in all groups. Cardiac index and PLVSP/LVESV significantly increased postoperatively in all groups, but did not in Group Ib. Angina disappeared postoperatively in 12 patients (92.3%) in group I and 16 (84.2%) in Group II. In both groups, NYHA classification was improved from class III or IV preoperatively to class I or II postoperatively. Postoperative 10 years actuarial survival rate was 90.7% in Group I and 90.8% in Group II. In conclusion, it was proved that CABG to TOLAD offered significant increase in left ventricular contractility, better quality of life and satisfactory long term survival rate almost same as CABG to POLAD.     

Improvement of myocardial function by trifluoperazine, a calmodulin antagonist, after acute coronary artery occlusion and coronary revascularization

Activation of an intracellular calcium-calmodulin complex may play an important role in myocardial injury induced by ischemia and reperfusion. Trifluoperazine, a calmodulin antagonist, was used before ischemia to enhance myocardial preservation by preventing intracellular calcium accumulation. The experimental model used an isolated in situ pig heart (19 control animals and 15 trifluoperazine-treated animals) subjected to occlusion of the left anterior descending coronary artery for 60 minutes followed by 60 minutes of hypothermic potassium crystalloid cardioplegic arrest and 60 minutes of reperfusion. Myocardial segmental function measured by ultrasonic crystals showed that active systolic segment shortening was abolished in the distribution of the left anterior descending artery after 60 minutes of occlusion irrespective of the treatment, whereas that not in the distribution of the left anterior descending artery increased by about 15% in both groups of animals. Restoration of systolic segment shortening in the distribution of the left anterior descending artery 60 minutes after reperfusion was 12% and 42% of baseline levels in untreated and trifluoperazine-treated animals, respectively (p less than 0.01). This improvement in segmental function by trifluoperazine was reflected in significantly (p less than 0.05) better global myocardial contractility and compliance and in significantly (p less than 0.01) greater total coronary blood flow and myocardial oxygen consumption. Trifluoperazine also increased myocardial creatine phosphate content in the distribution of the left anterior descending artery (p less than 0.01) during reperfusion, and creatine kinase release was reduced (p less than 0.05). Our results suggest that trifluoperazine improved regional myocardial function after acute occlusion of the left anterior descending artery and reperfusion and that global cardiac performance was thereby improved. The beneficial effects of trifluoperazine may be exerted by prevention of myocardial injury associated with the calcium-calmodulin complex in ischemic and reperfused myocardium.     

Effects of reperfusion after acute coronary occlusion on the beating, working heart compared to the arrested heart treated locally and globally with cardioplegia

To determine whether acutely ischemic myocardium could be more effectively salvaged by reperfusion on cardiopulmonary bypass (CPB) in the cardioplegia-treated heart than with reperfusion in the beating, working heart, 52 greyhound dogs underwent 3 hours of left anterior descending (LAD) occlusion and were randomly assigned to one of four groups. In Group I (19 dogs) the LAD occlusion was released at 3 hours and reperfusion continued in the beating, working heart for an additional 3 hours. Group II (six dogs), Group III (14 dogs), and Group IV (13 dogs) were placed on CPB and underwent 45 minutes of hypothermic ischemic arrest protected by aortic root potassium cardioplegia. In Group II, only aortic root potassium cardioplegia was given; in Group III, the ischemic area was perfused with potassium cardioplegic solution via a graft from the internal mammary artery (IMA) to the LAD. In Group IV, blood cardioplegic solution via the IMA-LAD graft was used. After the cross-clamp and local occlusion were removed, CPB was discontinued after an additional 45 minutes and reperfusion was continued off CPB for an additional 1 1/2 hours (total 6 hours). The ischemic area at risk was determined by injecting monastryl blue dye via the left atrium while the LAD was briefly reoccluded. After the animal had been sacrificed and the left ventricle had been sectioned, the area of myocardial necrosis was determined by nonstaining with triphenyltetrazolium chloride (TTC). For each group, the ratios of area of necrosis/area at risk (AN/AR) were calculated and postreperfusion arrhythmias were documented. Postreperfusion arrhythmias were noted in 11 of 12 animals in the beating, working heart group and only two of 24 in the combined CPB groups. The mean AN/AR was 66% +/- 2% in the beating, working heart (Group I), 59% +/- 6% after infusion of potassium cardioplegic solution into the aortic root (Group II), 57% +/- 6% with blood cardioplegia (Group IV), and 38% +/- 6.5% after global and local application of the potassium cardioplegic solution into the ischemic area (Group III). This study suggests that the reperfused ischemic myocardium will sustain less necrosis and less postreperfusion arrhythmias when the heart is protected by global and local cold potassium cardioplegia on CPB.     

Preconditioning of swine heart with monophosphoryl lipid A improves myocardial preservation

BACKGROUND: Ischemic preconditioning has been proven to be a powerful tool for myocardial protection in the setting of ischemia and reperfusion. A new drug to provide pharmacologic preconditioning, monophosphoryl lipid A (MLA), was administered 24 hours before an acute coronary occlusion in pigs to determine the effect on pharmacologic preconditioning. METHODS: Two studies were completed. In the first, swine were distributed into five groups: group I, control; group II,. aminoguanidine (AMG) (30 mg/kg), a selective inducible nitric oxide synthase (iNOS) blocker; group III, MLA (10 microg/kg); group IV, MLA (35 microg/kg); and group V, MLA and AMG (35 microg/kg and 30 mg/kg, respectively). Twenty-four hours after administration of the MLA, AMG, or both, regional left anterior descending coronary artery ischemia was induced for 15 minutes followed by one hour of global normothermic cardioplegic arrest and three hour reperfusion. Left ventricular function, tissue injury, and percentage of myocardial infarction were measured. Left ventricular myocardium in the left anterior descending coronary artery region was sampled for iNOS messenger RNA (mRNA) during ischemia and reperfusion. In the second study, pigs were sacrificed 0, 4, 6, 8, and 24 hrs after MLA/AMG administration for iNOS mRNA determination in nonischemic myocardium. RESULTS: Use of MLA significantly improved postischemic ventricular function, and reduced creatinine kinase release and percentage of infarction. Monophosphoryl lipid A induced expression of iNOS mRNA in nonischemic myocardium within four hours of administration which returned to base line by 24 hours. Normothermic regional ischemia then induced expression of iNOS mRNA, which returned to base line during reperfusion. Aminoguanidine completely abolished both MLA-induced and ischemia-induced iNOS mRNA and blocked the beneficial effects of MLA. CONCLUSIONS: Use of MLA can provide myocardial preservation through enhanced expression of iNOS mRNA.     

Effect of Shenfu injection on nuclear factor-kB during myocardial ischemia/reperfusion injury in rats

Objective: To investigate effects of Shenfu injection on the concentrations of plasma tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), activity of Nuclear Factor kappa B (NF-κB) and heart tissue ultrastructure during myocardial ischemia/reperfusion (I/R) injury in rats and its potential mechanism.Methods: Myocardial ischemia/reperfusion (I/R) was produced by ligation and release of the left anterior descending coronary artery. Ischemia lasted for 30 min and reperfusion for 60 min. Twenty-four healthy male SD rats weighing 230-280 g were randomly divided into three groups (n=8, each): Group I (Sham-operation group); Group II (I/R group); Group III (Shenfu group), in which Shenfu injection (10 ml/kg) was intraperitoneally injected 30 min before ischemia in animals with I/R. The plasma concentrations of IL-6 and TNF-α were measured by ELISA, and the heart was harvested for determination of NF-κB levels by Ecl-western blot analysis. Electron microscopy was used to study its ultrastructure.Results: After reperfusion, NF-κB binding activity in myocardial nuclei and the plasma concentrations of IL-6 and TNF-α were significantly increased in Group II, compared with Group I (P<0.01), and they were markedly reduced in Group III, compared with Group II (P<0.01). In addition, electron microscopic examination showed more serious injury of the myocardium ultrastructure in Group II, while in Group III the myocardial ultrastructure was similar to normal state.Conclusions: Shenfu injection inhibits NF-κB activity in I/R myocardium and leads to down-regulation of proinflammatory cytokine expression, which might be one of the molecular mechanisms of Shenfu injection in cardioprotection.     

A new method of retrograde cardioplegic administration. Right ventricular protection by right atrial perfusion cooling

Retrograde administration of cardioplegic solution via the right atrium with continuous cooling of the right ventricular cavity (right atrial perfusion cooling) was assessed for its protective effect in 12 dogs with occlusion of the right coronary artery subjected to global ischemia for 60 minutes. After an initial administration of 4 degrees C crystalloid cardioplegic solution by antegrade aortic perfusion, myocardial protection was established either by right atrial perfusion cooling (group I; n = 6) or by antegrade aortic perfusion alone (group II; n = 6). The right ventricular temperature was approximately 15 degrees C in group I and 20 degrees C in group II. After ischemia for 60 minutes, the adenosine triphosphate content of the right ventricular free wall was significantly higher in group I than in group II (24.4 +/- 1.45 versus 13.8 +/- 2.34 mumol/gm dry weight, p less than 0.05). The percent recovery of right ventricular contractility, which was evaluated by end-systolic pressure-volume relationships, was significantly better in group I at each reperfusion period (30 minutes: 130.0% +/- 9.6% versus 86.1% +/- 11.8%, p less than 0.05; 60 minutes: 159.6% +/- 12.9% versus 96.5% +/- 20.1%, p less than 0.05). Postischemic right ventricular stiffness (reciprocal value of compliance) increased in group II compared with group I, although the difference was not statistically significant. There were no major differences in percent recovery of the left ventricular end-systolic pressure-volume relationships between the two groups. The evidence suggests that the right atrial perfusion cooling method produces excellent right ventricular protection.     

Does hypothermic fibrillatory arrest improve myocardial protection during emergency revascularization?

Hypothermic fibrillatory arrest (HFA) was compared with conventional hypothermic cardioplegic arrest (HCA) in a model of acute regional ischemia. In 20 pigs, the left anterior descending coronary artery was occluded for 30 minutes before cardiopulmonary bypass. In the HCA group (n = 10), the heart was arrested with a hyperkalemic cold crystalloid solution, whereas in HFA animals (n = 10), the heart was vented and allowed to fibrillate spontaneously without cross-clamping. Miniature pH probes monitored intramyocardial pH during 45 minutes of arrest (HCA or HFA, both with systemic and topical myocardial cooling) and during two hours of coronary reperfusion. Hypothermic fibrillatory arrest did not ameliorate the acidosis in the ischemic (left anterior descending) region; indeed, after two hours of coronary reperfusion, there was a trend toward more acidosis in the postischemic left anterior descending territory in the HFA group. However, HFA did prevent acidosis in the nonischemic (left circumflex) territory. Infarct size expressed as percent of region at risk was 18.1% +/- 3.2% (mean +/- standard error of the mean) in the HCA animals and 18.8% +/- 4.4% in the HFA animals. These results demonstrate that HFA offers no advantage over HCA in protection of regionally ischemic myocardium in a model with minimal collateral circulation.     

Augmenting intracellular adenosine improves myocardial recovery

The objective of this study was to determine if augmentation of myocardial adenosine levels during global ischemia improves functional recovery after reperfusion. Isolated adult rabbit hearts were subjected to 120 minutes of mildly hypothermic ischemia (34 degrees C) with modified St. Thomas' Hospital cardioplegic solution used to provide myocardial protection. Myocardial adenosine levels were augmented during ischemia by providing exogenous adenosine in the cardioplegic solution or by inhibiting adenosine degradation with 2-deoxycoformycin, a noncompetitive inhibitor of adenosine deaminase. Four groups of hearts were studied: (1) control (n = 23)--cardioplegia alone; (2) adenosine group (n = 10)--adenosine 200 mumol/L added to the cardioplegic solution; (3) 2-deoxycoformycin group (n = 8)--2-deoxycoformycin 1 mumol/L added to the cardioplegic solution; and (4) a combined adenosine/deoxycoformycin group (n = 10). Recovery of developed pressure 45 minutes after reperfusion in the control group averaged only 38% +/- 4% of baseline values. Significantly better recovery was evident in the adenosine (66% +/- 7%), deoxycoformycin (59% +/- 2%), and adenosine/deoxycoformycin (75% +/- 2%) groups. The slope of the relationship between end-diastolic pressure and volume was used as an index of diastolic stiffness. The slope averaged 85 +/- 2 mm Hg/ml in the control group 45 minutes after reperfusion, significantly higher than that in the adenosine (31 +/- 6), deoxycoformycin (75 +/- 5), and adenosine/deoxycoformycin (58 +/- 5) groups; this suggests better diastolic function in the adenosine-augmented groups. During ischemia, adenosine levels were significantly elevated in the adenosine-augmented groups, whereas adenosine triphosphate decreased equally in all four groups, which indicates that augmenting myocardial adenosine had no effect on depletion of adenosine triphosphate during ischemia. After reperfusion, adenosine triphosphate levels were depressed in the control group but increased in the other groups above baseline values, which suggests that improvement in functional recovery was due to accelerated repletion of adenine nucleotide stores in the adenosine-augmented groups.     

Adjunctive left ventricular unloading during myocardial reperfusion plays a major role in minimizing myocardial infarct size

Although prompt institution of reperfusion following coronary artery occlusion has been shown to limit myocardial infarct size, significant "reperfusion injury" may result. We investigated in a canine model whether maintenance of the left ventricle in an unloaded state during the initial reperfusion period following acute myocardial ischemia would result in greater limitation of infarct size or modify the development of reperfusion injury. Group I (control, n = 6) underwent 6 hours of occlusion of the left anterior descending coronary artery without further intervention. In both Group II (n = 6) and Group III (n = 6), the snare was released after 2 hours and hearts were reperfused for 4 hours. In Group III only, the left ventricle was maintained in an unloaded state throughout the entire reperfusion interval via pulsatile left atrial-femoral artery bypass. The results showed that reperfusion of the left ventricle in an unloaded state resulted in significantly improved limitation of both infarct size (area of infarct/area at risk = 16.6% for Group III versus 72.0% for Group I and 55.4% for Group II, p less than 0.001) and area of microvascular damage (area of microvascular damage/area at risk = 4.8% for Group III versus 30.6% for Group II, p less than 0.001). These results indicate that although myocardial reperfusion of the type provided by thrombolysis and/or angioplasty techniques does result in limitation of infarct size when compared to no reperfusion, this limitation is not optimal unless the left ventricle is unloaded during the initial reperfusion period.