Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One hundred seven patients undergoing coronary artery bypass grafting were randomized to receive warm antegrade (n = 21), warm retrograde (n = 22), cold antegrade (n = 20), cold retrograde (n = 22), or intermittent cold antegrade (n = 22) blood cardioplegia. Myocardial oxygen consumption and lactate production, adenine nucleotides, and adenine nucleotide degradation products were measured during the operation, and creatine kinase-MB release was assessed postoperatively. Warm cardioplegia resulted in greater myocardial lactate production than cold cardioplegia (p = 0.048). Retrograde cardioplegia was associated with greater lactate production than antegrade cardioplegia (p = 0.015). Adenosine triphosphate depletion was similar among groups. However, poorly diffusible metabolites of adenosine triphosphate accumulated to the greatest extent in the intermittent cold group. Levels of hypoxanthine were highest after warm retrograde cardioplegia. Operative mortality and morbidity were low and were not different among groups. In summary, none of the five techniques of cardioplegia evaluated in this study was able to completely prevent myocardial ischemia. Anaerobic lactate production was minimized with cold cardioplegia and with antegrade cardioplegic delivery. Hypothermia may have impaired regeneration of adenosine triphosphate, however, particularly in association with inadequate or intermittent cardioplegic flow.
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PMID:Which techniques of cardioplegia prevent ischemia? 823 94

Both clinical and laboratory studies are being undertaken to investigate the deleterious neurologic and developmental effects associated with cardiopulmonary bypass, hypothermia, and circulatory arrest in the neonate and infant. A prospective, randomized clinical study of 171 neonates and young infants compared circulatory arrest with low-flow bypass (50 mL.kg-1.min-1). Circulatory arrest was associated with a higher incidence of early postoperative seizures as well as greater release of creatine kinase-BB. There was a strong correlation between duration of circulatory arrest and seizures (p = 0.004). The late consequences of these findings will be known at the completion of developmental assessment of all patients at 1 and 4 years of age. Laboratory studies have used a miniature piglet model that closely replicates clinical circulatory arrest. High-energy phosphate stores determined by magnetic resonance spectroscopy were maintained in animals undergoing 1 hour of low-flow bypass but became undetectable after 32 minutes of a 1-hour period of circulatory arrest. However, they returned to baseline within 3 hours of reperfusion as did cerebral blood flow and metabolism determined by microsphere studies. Piglets undergoing 1 hour of circulatory arrest showed more rapid recovery of cerebral adenosine triphosphate content and intracellular pH when managed with the pH-stat strategy during hypothermic bypass than with the more alkaline alpha-stat strategy. Other laboratory studies have examined pharmacologic methods of reducing cerebral injury associated with circulatory arrest including aprotinin, anti-CD18, neuronal receptor antagonists (MK801, NBQX), and blockade of glutamate release with adenosine in a cerebroplegia solution. These studies have suggested a number of promising approaches to improving the technique of circulatory arrest.
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PMID:Review of current research at Boston Children's Hospital. 826 70

We determined the influence of perfusate composition and reinfusion during ischemia upon myocardial protection in the immature rabbit heart. Isolated "working" hearts (n = 6 per group) from 7-10-day-old New Zealand White rabbits were perfused with Krebs bicarbonate buffer and function measured. Hearts were then arrested with 3 minutes cold (14 degrees C) perfusion with bicarbonate buffer (as hypothermia-alone group) or St. Thomas' II cardioplegic solution (as hypothermia-plus-cardioplegia group). Hearts were then subjected to hypothermic (14 degrees C) global ischemia for 2 or 6 hours, with and without multiple reinfusion of the coronary vasculature. Following 2 hours ischemia impaired recovery of aortic flow occurred after multiple reinfusion in comparison with a single infusion with the cardioplegic solution (64 +/- 3% versus 72 +/- 4%) but not with bicarbonate buffer (79 +/- 3% versus 83 +/- 4%). However after 6 hours ischemia impaired recovery of function occurred after multiple reinfusion in comparison with single infusion both with the cardioplegic solution (60 +/- 3% versus 68 +/- 3%) and with bicarbonate buffer (57 +/- 4% versus 75 +/- 5%). There were no differences in post-ischemic creatine kinase leakage or myocardial water content between groups. These results suggest (i) that reinfusion itself, regardless of the composition of the perfusate, caused decreased recovery of function after an extended period of ischemia, and (ii) protection of the ischemic immature heart with St. Thomas' II solution remains inadequate and requires improvement.
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PMID:Protection of the ischemic immature heart--effect of perfusate reinfusion and composition. 830 94

The effects of diltiazem, a sarcolemmal Ca2+ channel blocker, and ryanodine, an inhibitor of sarcoplasmic reticulum function, were investigated in isolated newborn rabbit hearts (2 to 5 days old) subjected to ischemia and reperfusion. After cardioplegic arrest with St. Thomas' Hospital solution, global ischemia was induced at 37 degrees C (normothermia) for 45 minutes or at 20 degrees C (hypothermia) for 180 minutes. The hearts were then reperfused at 37 degrees C for 30 minutes. Diltiazem or ryanodine, at concentrations that have minimal to moderately negative inotropic effects under nonischemic conditions, was added to the cardioplegic solution. After normothermic ischemia, reperfusion of untreated hearts resulted in recovery of left ventricular developed pressure to 52.9% +/- 2.5% of the preischemic level. In hearts treated with diltiazem, recovery of left ventricular developed pressure was significantly improved (84.2% +/- 2.9% at 3 x 10(-8) mol/L; p < 0.01). Comparable improvement was achieved with ryanodine (90.5% +/- 4.1% at 10(-9) mol/L; p < 0.01). Creatine kinase leakage and structural derangement of mitochondria were also reduced by both agents. With hypothermic ischemia, left ventricular developed pressure recovered in untreated hearts to 72.7% +/- 3.3% of preischemic values. Treatment with diltiazem improved the recovery of left ventricular developed pressure to 96.9% +/- 3.5% at 3 x 10(-8) mol/L and reduced creatine kinase leakage and mitochondrial damage. Ryanodine also improved the recovery of left ventricular developed pressure and attenuated ultrastructural damage. These findings suggest that Ca2+ handling by the sarcoplasmic reticulum, like transsarcolemmal Ca2+ influx, plays an important role in the pathogenesis of myocardial ischemia-reperfusion injury in the neonatal heart despite the morphologic and functional immaturity of the sarcoplasmic reticulum in the neonate.
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PMID:Protective effects of diltiazem and ryanodine against ischemia-reperfusion injury in neonatal rabbit hearts. 832 Oct 5

Supraventricular tachyarrhythmias following coronary artery bypass grafting are a common cause of postoperative morbidity, with a reported incidence of 10-40%. Two techniques of myocardial protection were assessed to determine their influence on the occurrence of postoperative supraventricular tachyarrhythmias. Group I (n = 82) received cold potassium cardioplegia combined with topical hypothermia and systemic cooling to 28 degrees C. Group II (n = 88) were protected by intermittent aortic cross-clamping with a systemic temperature of 32 degrees C. The overall incidence of atrial fibrillation/flutter was 22.3%. No significant difference was detected in the incidence of clinically important atrial fibrillation/flutter between the two groups [21/82 (25.6%) in group I versus 17/88 (19.3%) in group II, P > 0.25]. There was a positive association with age: in patients over 60 years the incidence of arrhythmias (31.8%) was significantly greater than in those less than 60 years (12.9%), P < 0.01. Sex, cardiopulmonary bypass times, aortic cross-clamp times, number of coronary grafts, end-operative creatine kinase myocardial band isoenzyme, right coronary endarterectomy and perioperative myocardial infarction had no association with the occurrence of postoperative atrial tachyarrhythmias.
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PMID:Atrial fibrillation after coronary artery bypass grafting: a comparison of cardioplegia versus intermittent aortic cross-clamping. 843 Dec 98

Deficiency of the enzymes of mitochondrial fatty acid oxidation and related carnitine dependent steps have been shown to be one of the causes of the fasting-induced hypoketotic hypoglycemia. We describe here carnitine-acylcarnitine translocase deficiency in a neonate who died eight days after birth. The proband showed severe fasting-induced hypoketotic hypoglycemia, high plasma creatine kinase, heartbeat disorder, hypothermia, and hyperammonemia. The plasma-free carnitine on day three was only 3 microM, and 92% of the total carnitine (37 microM) was present as acylcarnitine. Treatments with intravenous glucose, carnitine, and medium-chain triglycerides had been tried without improvements. Measurements in fibroblasts confirmed deficient oxidation of palmitate and showed normal activities of the carnitine palmitoyltransferases I and II and of the three acyl-CoA dehydrogenases. A total deficiency of the carnitine-acyl-carnitine translocase was found in fibroblasts using the carnitine acetylation assay (1986. Biochem. J. 236:143-148). This assay has been further simplified by seeking conditions permitting application to permeabilized fibroblasts and lymphocytes.
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PMID:Carnitine-acylcarnitine translocase deficiency with severe hypoglycemia and auriculo ventricular block. Translocase assay in permeabilized fibroblasts. 845 53

Hypothermic alkaline pharmacologic cardioplegia used in pediatric cardiac surgery may be less than satisfactory despite its benefits in adults. We determined whether the pH (7.8) of standard St. Thomas' II cardioplegic solution contributes to inadequate protection of the ischemic immature heart and whether the effect is age-related. Modified hypothermic St. Thomas' II solution (pH range, 4.8 to 8.8) was compared with hypothermic bicarbonate buffer alone (pH 7.25) in protecting the ischemic immature (7 to 10 days old) and mature (12 months old) rabbit heart. Isolated hearts (n = 6 per group) were perfused with bicarbonate buffer, and aortic flow was measured before hypothermic (14 degrees C) ischemia (immature hearts: 4 hours; mature hearts: 3 hours). Hearts were reperfused, and enzyme leakage and recovery of function were measured. In the immature heart, a bell-shaped dose-response profile was observed for pH and recovery of aortic flow but not for postischemic creatine kinase leakage. Optimal recovery of aortic flow (98% +/- 3%) occurred at pH 6.8, which was greater than protection with hypothermia alone (82% +/- 4%; p < 0.05) and standard St. Thomas' II solution (72% +/- 2%; p < 0.05). In the mature heart, a bell-shaped dose-response curve existed for recovery of aortic flow and a U-shaped curve existed for creatine kinase leakage. Again, optimal recovery of aortic flow (84% +/- 5%), which was superior to that with standard St. Thomas' II solution (60% +/- 8%; p < 0.05), and minimal enzyme leakage also occurred at pH 6.8, as did the least enzyme leakage (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Age and protection of the ischemic myocardium: is alkaline cardioplegia appropriate? 845 42

The effects of retrograde and antegrade delivery of cardioplegic solution on myocardial function were evaluated and compared in 60 patients who underwent myocardial revascularization. All patients had three-vessel coronary artery disease, and the revascularization was done with extensive use of the internal mammary artery. Seventy-five percent of the distal anastomoses were performed with the internal mammary artery. Myocardial protection consisted of St. Thomas' Hospital cardioplegic solution, topical slushed ice, and systemic hypothermia (28 degrees C). The patients were randomly separated into two groups: group A (n = 30), who received antegrade cardioplegia, and group B (n = 30), who received retrograde cardioplegia. With the exception of the total dose of cardioplegic solution (p = 0.02), there was no significant difference between the two groups that concerned septal myocardial temperature at the moment of asystole and after infusion of the total dose of cardioplegic solution. Cardiac function was assessed before and after the patient was weaned from cardiopulmonary bypass. In the immediate postoperative period there was a significant increase in right atrial pressure of the patients who underwent antegrade cardioplegia. For the other registered parameters there was no significant difference either in the immediate postoperative period or 6 hours later. Release of creatine kinase MB isoenzyme was the same in the two groups. Clinical outcome in terms of mortality, prevalence of perioperative infarction, prevalence of low cardiac output, and rhythm and conduction disturbances was similar in both groups. Technical problems related to cannulation and decannulation of the coronary sinus were not encountered. Multivariate analysis showed that occlusion of the left anterior descending coronary artery (p = 0.012) is an essential contraindication of antegrade delivery of cardioplegic solution. Analysis of the patients with an occlusion of the left anterior descending coronary artery who underwent antegrade (n = 9) and retrograde (n = 10) cardioplegia showed a significant difference in the total dose of cardioplegic solution (p = 0.02) and septal myocardial temperature at the moment of asystole (p = 0.008) and after infusion of the total dose of cardioplegic solution (p = 0.015). The mean arterial systolic blood pressure in the antegrade group was significantly lower than in the retrograde group (p = 0.003). Preservation of the left ventricular stroke work index was significantly better in the retrograde group (namely, 85% of its initial value versus 71% in the antegrade group, p = 0.0116).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Retrograde versus antegrade delivery of cardioplegic solution in myocardial revascularization. A clinical trial in patients with three-vessel coronary artery disease who underwent myocardial revascularization with extensive use of the internal mammary artery. 848 64

Uncontrollable hemorrhage accounts for a large proportion of total mortality in both civilian (31%) and military (47%) trauma victims. Hypothermia is a relatively safe method that could provide total body protection during hypovolemic shock and facilitate surgical intervention as a potentially life-saving procedure. This study tested the hypothesis that profound hypothermia and complete blood replacement in an established canine model, would facilitate resuscitative therapy from exsanguinating hypovolemic shock. Adult dogs were prepared for extracorporeal bypass using closed-chest peripheral cannulation under general anesthesia. Controlled hypotensive, hemorrhagic shock (mean arterial blood pressure < 50 mmHg) was induced for 30 min at normal temperature followed by temporary resuscitation using crystalloid infusion for approximately 10 min. Using our established procedure, the dogs were then cooled externally to 27 degrees C before initiating blood substitution with Hypothermosol (Cryomedical Sciences, Inc. Rockville, MD) via the extracorporeal pump. The heart was arrested during further cooling to below 10 degrees C and Hypothermosol was recirculated for 2 hr, with (3 dogs) or without (5 dogs) 1 hr of circulatory arrest. During rewarming the animals were autotransfused, weaned from the pump, and allowed to recover. All dogs (n = 8) survived, all but one with complete neurologic recovery: blood chemistry samples examined immediately after the procedure showed significant differences (p < 0.05) in only a few parameters, including creatine kinase (CK-BB and CK-MB), compared with the previous group of control dogs. The consistent survival of dogs showing apparently normal neurologic, physiologic, and biochemical recovery supports the concept that profound hypothermia using a protective hypothermic blood substitute could provide time for therapeutic resuscitation of currently intractable trauma cases.
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PMID:Hypothermic blood substitution enables resuscitation after hemorrhagic shock and 2 hours of cardiac arrest. 857 11

To date, ischemic preconditioning is regarded as the most powerful form of endogenous myocardial protection. For the purpose of surgical myocardial protection, a few clinical studies have investigated the effects of ischemic preconditioning in conjunction with hypothermia or blood cardioplegia during open heart surgery, but the results were controversial. We now tested the hypothesis that preconditioning improves myocardial protection in patients undergoing cold crystalloid cardioplegic arrest. 36 patients needing mitral prosthetic valve replacement for rheumatic heart disease were studied. Patients were evenly divided into two groups at random. Preconditioning was elicited by two cycles of 3 minutes ischemia by occlusion of vena cava and aortic cross-clamping followed by 2 minutes reperfusion under cardiopulmonary bypass. All hearts were arrested using 4 degrees C St. Thomas' Hospital solution before the intracardiac operative program. Myocardial protective effects were mainly assessed by electrocardiac activities, leakage of myocardial enzymes, myocardial contractility, and early postoperative recovery. The results indicated that there was a significant reduction of ST-segment shifting (ST-segment elevation, 0.07 +/- 0.02 vs 0.22 +/- 0.07 mV, p < 0.05, at 4 hours post reperfusion) and smaller release of creatine kinase-MB (87 +/- 11.5 vs 143 +/- 17.2 IU/L, p < 0.05, at 12 hours post reperfusion) in the preconditioning group. Preconditioning also enhanced myocardial contractility (dp/dtmax = 1490 +/- 75 vs 1280 +/- 88 mmHg/sec, at 30 minutes post reperfusion, p < 0.05) and promoted early postoperative recovery. The present study suggests that ischemic preconditioning reduces ischemia-reperfusion injury in human hearts even when combined with cold crystalloid cardioplegia.
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PMID:Preconditioning enhances myocardial protection in patients undergoing open heart surgery. 955 45


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