Biomedical subjects

R H Breyer

Publications and source records attributed to R H Breyer.

At least 19 recordsLinked to original sources

PubMed1989

Improvement of ischemia-reperfusion-induced myocardial dysfunction by modulating calcium-overload using a novel, specific calmodulin antagonist, CGS 9343B.

The present paper explores the mechanism of calcium-overloaded cardiac cell exocytosis during reperfusion of ischemic myocardium. A novel specific inhibitor of calmodulin, CGS 9343B, was used to pretreat an ischemic heart in an effort to enhance myocardial preservation. The experimental model employed an isolated in situ pig heart subjected to 120 min of ischemic insult by reversibly occluding the left anterior descending coronary artery, the last 60 min being superimposed with global hypothermic cardioplegic arrest. This ischemic episode was followed by 60 min of revascularization. CGS 9343B enhanced post-ischemic myocardial recovery, as judged by improved regional as well as global myocardial functions, better preservation of high-energy phosphate compounds, and reduced release of creatine kinase. Since this compound blocks calmodulin without inhibiting protein kinase C, the results of this study suggest that calmodulin-dependent kinase, rather than protein kinase C, is primarily involved in expressing calcium-overloaded cell exocytosis, and a specific calmodulin antagonist such as CGS 9343B can be used to salvage an ischemic heart from reperfusion injury.

Animals↗

PubMed1989

Steroid-induced myocardial preservation is associated with decreased cell membrane microviscosity.

Reperfusion of ischemic myocardium is associated with phospholipid degradation and corresponding changes in membrane fluidity. Dexamethasone (1.25 mg/kg i.v.) was evaluated in the pig, with pretreatment of the animal 1 1/2 hours before ischemic insult. The isolated perfused in vivo pig heart model was subjected to 60 minutes of regional ischemia of the left anterior descending coronary artery. The ischemic heart was then subjected to 60 minutes of global hypothermic cardioplegic arrest followed by 60 minutes of reperfusion, including reperfusion of the ischemic left anterior descending coronary artery region. Phospholipase A2, arachidonic acid, total free fatty acids, myocardial microviscosity, coronary blood flow, myocardial oxygen consumption, creatine kinase release, and regional and global myocardial function were measured. Dexamethasone pretreatment resulted in dramatic inhibition of phospholipase A2 activity accompanied by a reduction in arachidonic acid and total free fatty acid levels. Myocardial microviscosity (the inverse of membrane fluidity) was significantly increased only in untreated animals. Coronary blood flow and myocardial oxygen consumption were maintained at preischemic levels only in the dexamethasone-treated animals and were significantly reduced in the control group. Creatine kinase release increased nearly six times in control animals only while remaining stable in the dexamethasone-treated group, and regional and global myocardial contractility and compliance were improved dramatically in the dexamethasone-treated animals. These results indicate that dexamethasone enhances myocardial function by preserving membrane structure through inhibition of phospholipase activation, thereby preventing phospholipid degradation and maintaining membrane integrity and fluidity.

Animals↗

PubMed1989

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.

Adenosine Triphosphate↗

PubMed1988

Perioperative morbidity in diabetics requiring coronary artery bypass surgery.

We retrospectively evaluated the operative results in 384 patients with diabetes mellitus operated on for ischemic coronary artery disease over a six-year period compared with a random group of 396 patients selected from 2,069 nondiabetic patients who underwent operation during the same study period. In our analysis of 13 preoperative and 5 intraoperative variables, diabetics revealed a significantly increased incidence of hypertension (p less than 0.05) and a smaller proportion of men (p less than 0.05). All other variables were not significantly different. The incidence of perioperative myocardial infarction, renal failure, neurological sequelae, leg infections, or thromboembolic events was similar in diabetic and nondiabetic patients. Hospital stay, however, was significantly increased in the diabetic group (p less than 0.05). The diabetic patients requiring intraaortic balloon counterpulsation had a significantly higher incidence of all postoperative complications analyzed compared with diabetics without balloon support (p less than 0.01), whereas the nondiabetic subset requiring intraaortic balloon counterpulsation exhibited only a significantly higher incidence of renal failure (p less than 0.01) and neurological complications (p less than 0.05). These results indicate that diabetes per se does not significantly increase morbidity in coronary bypass surgery.

Coronary Artery Bypass↗

PubMed1988

Improved myocardial performance induced by clofibrate during reperfusion after acute myocardial infarction.

The increase of cellular fatty acids appears to be one of the causes of the myocardial injury during ischemia and reperfusion. This study was designed to examine whether a hypolipidemic drug such as clofibrate can reduce the myocardial injury during ischemia and reperfusion. Clofibrate was fed to experimental pigs for 9 days. Isolated in situ hearts from both experimental and control pigs were subjected to 60 min of regional ischemia induced by occluding the left anterior descending coronary artery, followed by 60 min of global ischemia by hypothermic cardioplegic arrest and 60 min of reperfusion. The clofibrate feeding resulted in the better cardiac performance as judged by increased coronary blood flow, improved left ventricular function, and reduced myocardial injury as judged by creatine kinase release. Although the clofibrate-fed animals contained higher levels of thiobarbituric reactive materials, the free fatty acid levels of plasma and myocardium were much lower compared with control animals. The clofibrate feeding was also associated with increased peroxisomal catalase and beta-oxidation of fatty acids. These results suggest that decreased levels of free fatty acids in the plasma and the myocardium and increased catalase activity induced by antilipolytic therapy appear to provide beneficial effects to the myocardium during ischemia and reperfusion.

Animals↗

PubMed1988

The effect of temperature and hematocrit level of oxygenated cardioplegic solutions on myocardial preservation.

The ideal temperature and hematocrit level of blood cardioplegia has not been clearly established. This study was undertaken (a) to determine the optimal temperature of blood cardioplegia and (b) to study the effect of hematocrit levels in blood cardioplegia. A comparison of myocardial preservation was done among seven groups of animals on the basis of variations in hematocrit levels and temperature of oxygenated cardioplegic solution. The experimental protocol consisted of a 2-hour hypothermic cardioplegic arrest followed by 1 hour of normothermic reperfusion. Group 1 received oxygenated crystalloid cardioplegic solution at 10 degrees C. Groups 2 through 7 received oxygenated blood cardioplegic solution with the following hematocrit values and temperatures: (2) 10%, 10 degrees C; (3) 10%, 20 degrees C; (4) 10%, 30 degrees C; (5) 20%, 10 degrees C; (6) 20%, 20 degrees C; and (7) 20%, 30 degrees C. Parameters studied include coronary blood flow, myocardial oxygen extraction, myocardial oxygen consumption, and myocardial high-energy phosphate levels of adenosine triphosphate and creatine phosphate during control (prearrest), arrest, and reperfusion. Myocardial oxygen consumption at 30 degrees C during arrest was significantly higher than at 10 degrees C and 20 degrees C, which indicates continued aerobic metabolic activity at higher temperature. Myocardial oxygen consumption and the levels of adenosine triphosphate and creatine phosphate during reperfusion were similar in all seven groups. Myocardial oxygen extraction (a measure of metabolic function after ischemia) during initial reperfusion was significantly lower in the 30 degrees C blood group than in the 10 degrees C blood group at either hematocrit level and in the oxygenated crystalloid group, which suggests inferior preservation. The hematocrit level of blood cardioplegia did not affect adenosine triphosphate or myocardial oxygen consumption or extraction. It appears from this study that blood cardioplegia at 10 degrees C and oxygenated crystalloid cardioplegia at 10 degrees C are equally effective. Elevating blood cardioplegia temperature to 30 degrees C, however, reduces the ability of the solution to preserve metabolic function regardless of hematocrit level. Therefore, the level of hypothermia is important in blood cardioplegia, whereas hematocrit level has no detectable impact, and cold oxygenated crystalloid cardioplegia is as effective as hypothermic blood cardioplegia.

Adenosine Triphosphate↗

PubMed1988

Enhanced myocardial preservation by nicotinic acid, an antilipolytic compound. Improved cardiac performance after hypothermic cardioplegic arrest.

The effect of nicotinic acid, an antilipolytic drug, on myocardial preservation was studied on the basis of cardiac performance after 2 hours of cardioplegic arrest. Isolated in situ pig hearts were subjected to 120 minutes of hypothermic potassium (35 mEq) crystalloid cardioplegic arrest followed by 60 minutes of reperfusion. The experimental group received nicotinic acid 0.08 mmol/L 15 minutes before cardioplegic arrest, whereas the control group received 15 minutes of unmodified perfusion. There was a marked decline in myocardial creatine phosphate levels during cardioplegic arrest in both groups that returned to the baseline level during reperfusion without a significant intergroup difference, and adenosine triphosphate levels remained stable throughout the experiment in both groups. Myocardial oxygen consumption during reperfusion was significantly higher in hearts treated with nicotinic acid, which was consistent with a significantly greater cardiac contractile force as evaluated by isovolumetric left ventricular pressure measurements. There appeared to be less cardiac membrane damage as measured by creatine kinase release during reperfusion, which was significantly inhibited by treatment with nicotinic acid. The present study supports the conclusion that nicotinic acid improves cardiac performance after hypothermic cardioplegic arrest.

Adenosine Triphosphate↗

PubMed1987

Transatrial repair of postinfarction posterior ventricular septal defect.

Repair of a postinfarction posterior ventricular septal defect generally has been performed by ventriculotomy in the infarct zone. This approach carries a significant mortality and morbidity from hemorrhage, extending infarction, or further compromise of ventricular function secondary to suture placement. A successful transatrial repair of a postinfarction posterior ventricular septal defect is presented. The simplicity of this operation and the patient's rapid recovery contrasted remarkably with the transventricular approach used in previous patients.

Coronary Artery Bypass↗

PubMed1987

Age-related development profiles of the antioxidative defense system and the peroxidative status of the pig heart.

The developmental profiles of the antioxidative defense system and the peroxidative status of the heart during growth and development were studied in pigs of three different age groups. A unique age-specific myocardial lipid peroxidation expressed in terms of malonaldehyde formation occurred after incubation of neonatal and adult pig heart homogenates in the absence of any added factors. Very little malonaldehyde release was noticed in the 0- to 2-day age group, while considerably higher activity was found in the 8- to 10-day-old animals. The 2-month-old pig heart again formed very little malonaldehyde. Myocardial injury from lipid peroxidation was highest in the 0- to 2-day age group, as evidenced by the release of oxidized glutathione, lactate dehydrogenase (LDH) and creatine kinase (CK) activities. Release of glutathione, LDH and CK decreased with age and was minimal in the adult group. The antioxidative enzymes, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, increased during the first 10 days of neonatal growth and then levelled off. Glucose-6-phosphate dehydrogenase was present in appreciably lower amounts in adult hearts compared to neonatal hearts. Heart weight increased with aging, but myocardial water content decreased. Protein and DNA contents of hearts increased with age, such that the protein/DNA ratio almost doubled from the newborn to adult age. The results indicate that the newborn pig hearts are equipped with the antioxidative defense system, which undergoes significant development during the initial phase of neonatal growth and does not change appreciably thereafter. The results further suggest that the change in activity profile with aging is different for different enzymes, and the peroxidative status of the myocardium is not a function of these enzyme activities.

Aging↗

PubMed1987

Blood conservation for myocardial revascularization. Is it cost effective?

A total of 284 patients undergoing myocardial revascularization were prospectively studied to determine if the use of intraoperative autotransfusion or intraoperative autotransfusion plus postoperative reinfusion of shed mediastinal blood decreased transfusion requirements and the use of one or both techniques was cost effective. The Haemonetics Cell Saver System was used for intraoperative autotransfusion and the Sorenson Receptaseal autotransfusion system for postoperative reinfusion of shed mediastinal blood. During Phase 1, the Cell Saver System was used for 57 patients and 93 patients served as a control group. During Phase 2, the Cell Saver System plus the autotransfusion system were used in 43 patients and 91 patients were in the control group. Separate parallel analyses to compare the blood conservation groups to control groups were conducted for each phase of the study. The patient groups were comparable with regard to age, sex, preoperative red cell mass, preoperative hematocrit value, number of bypasses, and use of internal mammary grafts. Blood conservation techniques resulted in significant reductions in the use of bank blood. During Phase 1, Cell Saver System patients received an average of 2.8 units of packed cells versus 4.7 units for control patients. Transfusion was avoided entirely in 14% of Cell Saver System patients compared to 3% of control patients. During Phase 2, patients subjected to both the Cell Saver System and the autotransfusion system received an average of 1 unit of packed red cells versus 3 units for control patients. Transfusion was required in only 42% of patients subjected to both the Cell Saver System and the autotransfusion system compared to 85% of control patients. Multiple logistic regression analysis confirmed that the use of the Cell Saver System in Phase 1 and the Cell Saver System and autotransfusion system in Phase 2 were each independently predictive of decreased transfusion requirements. The total "blood-related costs" (including cost for all bank blood products plus Receptaseal and Cell Saver System equipment) was slightly lower for the blood conservation patients in both Phase 1 ($555.00 versus $615.00, no significant difference) and Phase 2 ($373.00 versus $426.00, no significant difference). Intraoperative use of the Cell Saver System is associated with substantial savings of bank blood, and the addition of postoperative reinfusion of shed mediastinal blood results in further bank blood savings. The use of blood conservation techniques is cost effective; that is, the costs incurred for the blood conservation equipment are more than offset by the resultant dollar savings for blood products.

Blood Transfusion, Autologous↗

PubMed1987

Catheter drainage of symptomatic postoperative mediastinal effusion guided by computed tomography. A nonoperative approach.

Postoperative mediastinal effusion after cardiac operations is a common phenomenon and has a potential for serious complications, such as tamponade necessitating urgent drainage. Computed tomography of the chest provides excellent postoperative visualization of the mediastinum. Catheter insertion or paracentesis guided by computed tomography has been used to accomplish nonoperative drainage of symptomatic postoperative mediastinal effusion in six cases. This technique offers simplicity, safety, and cost effectiveness.

Aged↗

PubMed1987

Aerobic vs anaerobic metabolism during ischemia in heart muscle.

Anaerobic metabolism in heart muscle plays a role in maintenance of myocardial preservation only during ischemia or hypoxia. In an ischemic state, such as during a heart attack or even during the induced ischemia of open heart surgery, there is impairment of blood flow to the myocardium. The major energy-yielding process in the heart is through the metabolism of glucose and lipids by oxidative reactions. Under anaerobic conditions, oxygen is not available to accept the electrons in the metabolic degradation of substrates and anaerobic glycolysis becomes important in the preservation of myocardial viability during the ischemic process. Unfortunately, the accumulated products of glycolysis, namely protons and lactate, work to inhibit glycolysis, ultimately resulting in a depression of anaerobic metabolism. Cardioplegia, as utilized during open heart surgery, has the effect of inducing instantaneous induction of myocardial mechanical and electrical arrest with a maximal inhibition of the energy utilizing metabolic processes. This effectively reduces substrate utilization and prevents the deleterious consequences of the ischemic process. Cardioplegia is most effective when combined with the additive properties of hypothermia, which plays a significant role in decreasing myocardial metabolism. However, during prolonged hypothermic cardioplegic arrest, sufficient ATP cannot be maintained for cellular integrity and anaerobic glycolysis becomes of increasing importance for maintenance of myocardial preservation. This presentation deals with the mechanics of aerobic versus anaerobic metabolism during the ischemic process of open heart surgery.

Adenosine Triphosphate↗

PubMed1987

The mechanism of myocardial reperfusion injury in neonates.

Oxygen free radicals and phospholipid degradation have been implicated in the pathogenesis of ischemia and reperfusion injury. The present study examines the involvement of such mechanisms in myocardial reperfusion injury in neonatal hearts. The isolated neonatal pig hearts from two different age groups, 0 to 2 days old (newborn) and 7 to 9 days old (week-old), were subjected to 60 min of normothermic global ischemia followed by 60 min of reperfusion. Although myocardial ischemia reduced superoxide dismutase, catalase, and glutathione peroxidase activities in both age groups, superoxide dismutase and catalase activities remained significantly lower in the newborn pig heart during ischemia and reperfusion. Oxidized glutathione release from the neonatal pig hearts was at minimum levels before ischemia, but it increased 10-fold at the onset of reperfusion and was significantly higher in the newborn heart. This indicates that generation of oxygen free radicals was enhanced in the newborn compared with that in the week-old heart. The increase in phospholipase A2 activity and decrease in acyl CoA synthetase and lysophosphatidylcholine acyl transferase activities during ischemia and reperfusion were associated with comparable loss of membrane phospholipids and accumulation of lysophosphatidylcholine and free fatty acids in both age groups, except that oleic acid content was significantly higher in the newborn heart during reperfusion. Myocardial damage appears to be potentiated in the newborn heart during reperfusion, as evidenced by higher release of creatine kinase and a lower content of high-energy phosphates. These results indicate that oxygen free radicals may play a crucial role in the occurrence of reperfusion injury in immature hearts.

Animals↗

PubMed1986

Enhanced prostaglandin synthesis due to phospholipid breakdown in ischemic-reperfused myocardium. Control of its production by a phospholipase inhibitor or free radical scavengers.

The effects of the inhibition of phospholipid degradation and superoxide radical generation on prostaglandin synthesis associated with myocardial ischemia and reperfusion were studied in the isolated, in-situ pig heart model subjected to 60 mins of regional ischemia and a further 60 mins of hypothermic potassium cardioplegic arrest, followed by 60 mins of reperfusion. Myocardial biopsies were taken from the ischemic and non-ischemic regions of the myocardium for measurement of phospholipids, and samples of the perfusate were drawn for estimation of the end-products of arachidonic acid metabolism, 6-keto-prostaglandin-F1 alpha and thromboxane B2. A significant amount of 6-keto-prostaglandin F1 alpha and thromboxane B2 appeared during reperfusion, corresponding with the loss of membrane phospholipids in control animals. Mepacrine, a phospholipase inhibitor, protected the depletion of membrane phospholipids and inhibited the products of arachidonate metabolism. Superoxide dismutase (SOD) and catalase, on the other hand, enhanced the formation of 6-keto-prostaglandin F1 alpha and thromboxane B2. The effects of both mepacrine and the free radical scavengers were pronounced during the reperfusion phase when the most significant depletion in membrane phospholipids occurred. These results suggest that the arachidonate cascade is activated during reperfusion of ischemic myocardium as a consequence of phospholipid breakdown, and this activation can be attenuated by inhibiting phospholipases or enhanced by scavenging oxygen-free radicals generated during reperfusion.

6-Ketoprostaglandin F1 alpha↗

PubMed1986

Role of membrane phospholipids in myocardial injury induced by ischemia and reperfusion.

Depletion of membrane phospholipids is known to be associated with myocardial ischemia, but its relationship to the injury involved with the reperfusion of ischemic myocardium is not known. The present study was designed to relate phospholipid degradation with reperfusion injury. The isolated in situ pig heart was subjected to 60 min of regional ischemia induced by occluding the left anterior descending (LAD) coronary artery and 60 min of global ischemia by hypothermic cardioplegic arrest followed by 60 min of reperfusion. The pigs were divided into two groups. In the treatment group, the heart was preperfused with mepacrine (0.05 mM), a known phospholipase inhibitor, for 15 min prior to LAD occlusion. In the control group, the total phospholipid content was not significantly decreased during LAD occlusion and arrest, but was reduced appreciably after reperfusion. Phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol followed a similar pattern. The lowering of these phospholipids during reperfusion was accompanied by enhancement of lysophosphatidylcholine. Mepacrine restored the normal levels of these phospholipids. During reperfusion, fatty acyl CoA synthetase, lysophospholipase, and lysophosphatidylcholine acyltransferase were depressed, whereas phospholipase A2 was enhanced. Mepacrine inhibited phospholipase A2, but had no effects on the other enzymes. Mepacrine also provided significant protection against reperfusion injury, as documented by the preservation of high-energy phosphate compounds and inhibition of the appearance of creatine kinase activity in the perfusate. These results suggest that membrane phospholipids play an important role in myocardial injury associated with ischemia and reperfusion, primarily because the deacylation-reacylation cycle of phospholipid biosynthesis becomes defective.

1-Acylglycerophosphocholine O-Acyltransferase↗

PubMed1986

Effect of superoxide dismutase and catalase on myocardial energy metabolism during ischemia and reperfusion.

Survival of cardiac patients undergoing heart surgery depends critically upon the recovery of myocardial energy metabolism during reperfusion of ischemic myocardium. The present study compares various parameters of myocardial energy metabolism using an isolated in situ pig heart. The left anterior descending (LAD) coronary artery was occluded for 60 min, followed by 60 min of global hypothermic cardioplegic arrest and 60 min of reperfusion. Free radical scavengers [superoxide dismutase SOD and catalase] were used to protect the ischemic heart from reperfusion injury. In both control and SOD plus catalase-treated groups, ATP, creatine phosphate (CP), ATP/ADP ratio, energy charge and phosphorylation potential dropped significantly during ischemic insult. After reperfusion, CP, ATP/ADP ratio and phosphorylation potential improved significantly, but they were restored to control level only in treated animals. In either case, free energy of ATP hydrolysis (delta G) lowered only by 5% during ischemia, but recovered promptly upon reperfusion. SOD and catalase also improved coronary blood flow and reduced creatine kinase release compared to those of untreated animals, suggesting improved myocardial recovery upon reperfusion. Our results suggest that SOD and catalase significantly improve the myocardial recovery during reperfusion by enhancing rephosphorylation steps, and the value of delta G is more critical compared to those of ATP and CP for myocardial recovery.

Adenosine Triphosphate↗

PubMed1986

Mepacrine, a phospholipase inhibitor. A potential tool for modifying myocardial reperfusion injury.

Cardioprotective effects of phospholipase inhibitor, mepacrine, on ischemic reperfused myocardium were investigated in the isolated in situ pig heart preparation, which was subjected to 120 minutes of regional ischemia, with the final 60 minutes having superimposed global cardioplegic arrest followed by 60 minutes of reperfusion. Mepacrine (0.05 mmol/L) was administered before ischemia into the perfusion circuit in 15 of 29 experiments. Significant depletion of myocardial phospholipids occurred in nontreated animals during 60 minutes of reperfusion. Mepacrine prevented the reperfusion-induced phospholipid degradation. Further, the level of high-energy phosphate compounds was higher during ischemia and reperfusion in the mepacrine-treated hearts. Left ventricular developed pressure, maximum rate of rise of left ventricular pressure, and left ventricular end-diastolic pressure were measured under isovolumic conditions to assess cardiac contractility and compliance. During incubation with mepacrine, before ischemia, left ventricular developed pressure and maximum rate of rise of left ventricular pressure decreased to 45% and 51% of baseline values, respectively. This initial decline was improved to 65% and 70% in mepacrine-treated animals during the early period of regional ischemia. In the nontreated control heart, a progressive decline in contractility was observed with ischemia such that no significant difference was apparent in the two groups. Reperfusion resulted in a further deterioration of global cardiac performance in both mepacrine-treated and control animals. Although pretreatment with mepacrine did not improve contractility, myocardial oxygen consumption, coronary flow, and cardiac compliance significantly improved. These results suggest that myocardial injury may develop during reperfusion after temporary ischemia. Mepacrine inhibits such injury by acting as a phospholipase inhibitor, but it also behaves as a negative inotropic agent in ischemic reperfused myocardium.

Animals↗

PubMed1986

Metabolic enhancement of myocardial preservation during cardioplegic arrest.

An experimental study was undertaken to evaluate the relative efficacy of oxygenated versus unoxygenated cardioplegic solutions and to determine if the addition of certain metabolically active substrates to cardioplegic solutions had any effect on myocardial preservation. Sixty-one pigs were divided into seven groups of animals (5 to 15 animals per group). The impact of different cardioplegic vehicles, i.e., crystalloid versus the oxygen-carrying vehicles, blood and Fluosol-DA, on preservation of high-energy phosphates (adenosine triphosphate and creatine phosphate) was examined in the first three animal groups. The influence of Krebs cycle intermediates, i.e., glutamate, malate, succinate and fumarate, on adenosine triphosphate and creatine phosphate preservation was evaluated in the other four animal groups. All hearts underwent 120 minutes of hypothermic cardioplegic arrest at 15 degrees C followed by 60 minutes of normothermic reperfusion. Higher adenosine triphosphate and creatine phosphate levels were maintained during arrest when oxygenated solutions were used as the cardioplegic vehicle and when any of the four intermediates were added to the crystalloid cardioplegic solution, especially succinate and fumarate. During reperfusion, however, adenosine triphosphate levels were uniformly lower than control whereas creatine phosphate levels rose to either control levels or higher in all groups. No significant intergroup difference could be identified during reperfusion. These findings lead to the conclusion that the presence of either oxygen or certain Krebs cycle intermediates enhances the protective effect of hyperkalemic hypothermic cardioplegia on high-energy phosphates during the arrest period only. This enhancement is not maintained during the reperfusion period.

Adenosine Triphosphate↗