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

The extent of myocardial protection afforded by a procaine cardioplegic solution during cardiac ischemia has been evaluated and compared with the protection seen using a potassium cardioplegic solution. An isolated cat heart model was employed, and ventricular function parameters, intramyocardial gas tensions, and postischemic myocardial edema were measured and compared following 60 minutes of induced ischemia at 37 degrees C. and 27 degrees C. There was no significant improvement in recovery of postarrest ventricular function when procaine cardioplegia was used during normothermic ischemia. When used at 27 degrees C., however, both cardioplegic solutions were associated with significantly better recovery of postarrest ventricular function, although there was less myocardial edema formation in the potassium-treated hearts. Results of this study indicate that procaine-induced cardioplegia provides myocardial protection during anoxic cardiac arrest which is additive to that afforded by hypothermia alone. In addition, procaine cardioplegia results in postarrest functional recovery which is similar to that seen with potassium cardioplegia.
 ...
PMID:Effects of procaine-induced cardioplegia on myocardial ischemia, myocardial edema, and postarrest ventricular function. A comparison with potassium-induced cardioplegia and hypothermia. 66 57

Isolated perfused working rat hearts were subjected to elective cardiac arrest for 20 or 30 min. Various methods of arrest were studied, either singly or in combination and with or without coronary perfusion. The functional recovery of the heart following the termination of arrest was found to be related to the concentration of ATP and creatine phosphate in the myocardium at the end of the period of arrest. In turn, these concentrations were dependent upon the method used to induce arrest. Normothermic ischemic arrest led to a marked reduction in high energy phosphates and a poor functional recovery. In contrast, coronary perfusion with hypothermic solutions or solutions containing high concentrations of potassium, induced arrest without depleting ATP or creatine phosphate. These procedures conferred considerable protection on the myocardium and thus permitted good recoveries. The energy status and recovery associated with ischemic arrest could be improved by combining the ischemia with hypothermia or potassium arrest. The latter, while increasing recovery significantly, still failed to afford complete protection to the myocardium. Potassium chloride gave greater protection than potassium citrate. When topical hypothermia was combined with ischemia, a time and temperature relationship was demonstrated but effective protection could only be obtained with severe topical hypothermia over a relatively short time period. The results stress the importance of maintaining high energy phosphates during arrest, and this requires the provision of a continuous supply of oxygen and nutrient, which may perhaps be best achieved by ensuring continuous and adequate coronary perfusion.
 ...
PMID:Ischemic damage and metabolism during elective cardiac arrest. 120 80

Temperature is known to influence the extent of anoxic/ischemic injury in gray matter of the brain. We tested the hypothesis that small changes in temperature during anoxic exposure could affect the degree of functional injury seen in white matter, using the isolated rat optic nerve, a typical CNS white matter tract (Foster et al., 1982). Functional recovery after anoxia was monitored by quantitative assessment of the compound action potential (CAP) area. Small changes in ambient temperature, within a range of 32 to 42 degrees C, mildly affected the CAP of the optic nerve under normoxic conditions. Reducing the temperature to < 37 degrees C caused a reversible increase in the CAP area and in the latencies of all three CAP peaks; increasing the temperature to > 37 degrees C had opposite effects. Functional recovery of white matter following 60 min of anoxia was strongly influenced by temperature during the period of anoxia. The average recovery of the CAP, relative to control, after 60 min of anoxia administered at 37 degrees C was 35.4 +/- 7%; when the temperature was lowered by 2.5 degrees C (i.e., to 34.5 degrees C) for the period of anoxic exposure, the extent of functional recovery improved to 64.6 +/- 15% (p < 0.00001). Lowering the temperature to 32 degrees C during anoxic exposure for 60 min resulted in even greater functional recovery (100.5 +/- 14% of the control CAP area). Conversely, if temperature was increased to > 37 degrees C during anoxia, the functional outcome worsened, e.g., CAP recovery at 42 degrees C was 8.5 +/- 7% (p < 0.00001). Hypothermia (i.e., 32 degrees C) for 30 min immediately following anoxia at 37 degrees C did not improve the functional outcome. Many processes within the brain are temperature sensitive, including O2 consumption, and it is not clear which of these is most relevant to the observed effects of temperature on recovery of white matter from anoxic injury. Unlike the situation in gray matter, the temperature dependency of anoxic injury cannot be related to reduced release of excitotoxins like glutamate, because neurotransmitters play no role in the pathophysiology of anoxic damage in white matter (Ransom et al., 1990a). It is more likely that temperature affects the rate of ion transport by the Na(+)-Ca2+ exchanger, the transporter responsible for intracellular Ca2+ loading during anoxia in white matter, and/or the rate of some destructive intracellular enzymatic mechanism(s) activated by pathological increases in intracellular Ca2+.
 ...
PMID:Effects of temperature on evoked electrical activity and anoxic injury in CNS white matter. 140 Jun 52

A significant reduction in the extent of cell necrosis or the incidence of reperfusion-induced arrhythmias can be achieved with ischaemic preconditioning. If preconditioning was also found to be effective in protecting against global ischaemia, then this may have significant implications for the preservation of the heart during cardiac surgery. We therefore investigated this phenomenon in relation to recovery of contractile function after global ischaemia in the isolated rat heart. Isolated working rat hearts (n = 6 per group) were perfused aerobically at 37 degrees C for 20 min and contractile function recorded. This was followed by 10 min of aerobic Langendorff perfusion (control hearts) or 5 min global ischaemia (37 degrees C) + 5 min Langendorff reperfusion (preconditioned hearts). The hearts were then subjected to 10, 15, 20 or 25 min of global ischaemia (37 degrees C) and reperfusion (15 min Langendorff + 20 min working) after which function was again assessed. Preconditioning improved functional recovery after all durations of ischaemia. Thus aortic flow after 10, 15, 20 and 25 min of ischaemia and 35 min of reperfusion recovered to 84, 58, 16 and 5%, respectively, in controls and 88, 74, 55 and 20%, respectively, in the preconditioned groups. To assess whether preconditioning was effective in a surgically relevant model of hypothermic ischaemia, the experiments were repeated with longer periods (45, 70, 90, 115, 135 and 160 min) of ischaemia at 20 degrees C. Under these conditions, normothermic preconditioning increase the post-ischaemic recovery of aortic flow after 115, 135 and 160 min of ischaemic (from 36, 20 and 10%, respectively, in controls to 57, 39 and 26%, respectively, in preconditioned hearts). There was no consistent correlation between tissue high energy phosphate content and enhanced post-ischaemic recovery. Thus, we have demonstrated that ischaemic preconditioning can improve contractile function after global ischaemia in the isolated rat heart, we have defined the duration of ischaemia for which it is operative, and we have shown that this protection is additive to that of hypothermia-induced protection during ischaemia. This may have clinical implications for cardiac surgery.
 ...
PMID:Ischaemic preconditioning and contractile function: studies with normothermic and hypothermic global ischaemia. 147 13

Working rat hearts were perfused for 15 minutes at 37 degrees C before switching to a Langendorff perfusion (60 mm Hg aortic pressure) at 10 degrees C for 40 minutes of hypothermic arrest. Ventricular function was allowed to recover for 15 minutes at 37 degrees C by reestablishing the prehypothermic conditions. The perfusate was Krebs-Henseleit bicarbonate buffer containing 3% bovine serum albumin and either glucose (11 mmol/L) or glucose (11 mmol/L) plus palmitate (1.2 mmol/L) and gassed with 95% O2 and 5% CO2. In hearts receiving glucose alone as substrate, coronary flow was maintained constant during the 40 minutes of hypothermic arrest and returned to prehypothermic rates with rewarming. Ventricular function, as estimated by peak systolic pressure and heart rate, recovered to the prehypothermic level. When palmitate was added, coronary flow decreased continuously throughout the hypothermic perfusion (22% decrease by 40 minutes), and ventricular pressure development was lower throughout the rewarming perfusion. Tissue levels of adenosine triphosphate and creatine phosphate were well maintained and long-chain acyl coenzyme A and acyl carnitine decreased during hypothermia regardless of the substrate provided. With rewarming, tissue levels of adenosine triphosphate and creatine phosphate decreased in those hearts receiving palmitate. Omission of fatty acid either during hypothermia or during the first 5 minutes of rewarming improved recovery of function. Addition of oxfenicine to inhibit fatty acid oxidation, or inhibition of Ca2+ overload by verapamil and low perfusate Ca2+, prevented the effects of palmitate on ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Fatty acids suppress recovery of heart function after hypothermic perfusion. 192 62

Clinical application of hypothermic pharmacologic cardioplegia in pediatric cardiac surgery is less than satisfactory, despite its well known benefits in adults. Protection of the ischemic immature rabbit heart with hypothermia alone is better than with hypothermic St. Thomas' II cardioplegic solution. Control of cellular calcium is a critical component of cardioplegic protection. We determined whether the existing calcium content of St. Thomas' II solution (1.2 mmol/L) is responsible for suboptimal protection of the ischemic immature rabbit heart. Modified hypothermic St. Thomas' II solutions (calcium content, 0 to 2.4 mmol/L) were compared with hypothermic Krebs bicarbonate buffer in protecting ischemic immature (7- to 10-day-old) hearts. Hearts (n = 6 per group) underwent aerobic "working" perfusion with Krebs buffer, and cardiac function was measured. The hearts were then arrested with a 3-minute infusion of either cold (14 degrees C) Krebs buffer (1.8 mmol calcium/L) as hypothermia alone or cold St. Thomas' II solution before 6 hours of hypothermic (14 degrees C) global ischemia. Hearts were reperfused, and postischemic enzyme leakage and recovery of function were measured. A bell-shaped dose-response profile for calcium was observed for recovery of aortic flow but not for creatine kinase leakage, with improved protection at lower calcium concentrations. Optimal myocardial protection occurred at a calcium content of 0.3 mmol/L, which was better than with hypothermia alone and standard St. Thomas' II solution. We conclude that the existing calcium content of St. Thomas' II solution is responsible, in part, for its damaging effect on the ischemic immature rabbit heart.
 ...
PMID:Calcium content of St. Thomas' II cardioplegic solution damages ischemic immature myocardium. 192 65

A prospective randomized controlled trial was performed to determine optimal flow rates and hemoglobin concentrations for continuous normothermic blood cardioplegia and to compare warm heart surgery with standard intermittent cold blood cardioplegia. Thirty-five patients received intermittent cold blood cardioplegia, low hemoglobin low flow, low hemoglobin high flow, high hemoglobin low flow, or high hemoglobin high flow warm blood cardioplegia (seven patients per group: low hemoglobin, 50 g/l; high hemoglobin, 80 g/l; low flow, less than 80 ml/min; high flow, greater than 80 ml/min). Hypothermia resulted in a significantly greater accumulation of ADP and AMP during cross clamp, consistent with impaired mitochondrial function. Low hemoglobin low flow warm blood cardioplegia increased myocardial oxygen consumption and coronary sinus blood flow after cross clamp release, and also decreased lactate consumption. Postoperative myocardial performance and diastolic compliance were reduced in low hemoglobin low flow warm patients, and diastolic compliance was increased with high hemoglobin high flow warm blood cardioplegia when compared with cold patients. In this study, continuous normothermic cardioplegia was safe when delivered at 80 ml/min or greater, with a hemoglobin concentration of at least 80 g/l, affording myocardial metabolic and functional recovery comparable to that found after intermittent cold blood cardioplegia.
 ...
PMID:Optimal delivery of blood cardioplegia. 193 34

The concentration of calcium (1.2 mmol/L) in clinical St. Thomas' Hospital cardioplegic solution was chosen several years ago after dose-response studies in the normothermic isolated heart. However, recent studies with creatine phosphate in St. Thomas' Hospital solution demonstrated that additional myocardial protection during hypothermia resulted principally from its calcium-lowering effect in the solution. The isolated working rat heart model was therefore used to establish the optimal calcium concentration in St. Thomas' Hospital solution during lengthy hypothermic ischemia (20 degrees C, 300 minutes). The calcium content of standard St. Thomas' Hospital solution was varied from 0.0 to 1.5 mmol/L in eight treatment groups (n = 6 for each group). During ischemia, hearts were exposed to multidose cardioplegia (3 minutes every 30 minutes). Postischemic recovery of function was expressed as a percentage of preischemic control values. Release of creatine kinase and the time to return of sinus rhythm during the reperfusion period were also measured. These dose-response studies during hypothermic ischemia revealed a broad range of acceptable calcium concentrations (0.3 to 0.9 mmol/L), which appear optimal in St. Thomas' Hospital solution at 0.6 mmol/L. This concentration improved the postischemic recovery of aortic flow from 22.0% +/- 5.9% with control St. Thomas' Hospital solution (calcium concentration 1.2 mmol/L) to 86.0% +/- 4.0% (p less than 0.001). Other indices of functional recovery showed similar dramatic results. Creatine kinase release was reduced 84% (p less than 0.01) in the optimal calcium group. Postischemic reperfusion arrhythmias were diminished with the loser calcium concentration, with a significant decrease in the time between initial reperfusion until the return of sinus rhythm. In contrast, acalcemic St. Thomas' Hospital solution precipitated the calcium paradox with massive enzyme release and no functional recovery. Unlike prior published calcium dose-response studies at normothermia, these results demonstrate that the optimal calcium concentration during clinically relevant hypothermic ischemia is considerably lower than that of normal serum ionized calcium (1.2 mmol/L) and appears ideal at 0.6 mmol/L to realize even greater cardioprotective and antiarrhythmic effects with St. Thomas' Hospital solution.
 ...
PMID:Lowering the calcium concentration in St. Thomas' Hospital cardioplegic solution improves protection during hypothermic ischemia. 199 42

In the neonatal rabbit heart, multidose crystalloid cardioplegia is protective against normothermic ischemia, but its beneficial effects are lost under hypothermia. In order to determine the relationship between myocardial protection and the number of cardioplegic infusions administered during the ischemic period, we examined the effects of an increasing number of infusions on postischemic recovery at three temperatures (37 degrees, 20 degrees, or 10 degrees C). Isolated working hearts from rabbits aged 7-10 days were perfused aerobically (37 degrees C) for 20 min before infusion of St. Thomas' Hospital cardioplegic solution at the selected temperature. At each temperature, the cardioplegic solution was given either as a single 2-min infusion (single-dose) or as repeated 2-min infusions (multidose) at various intervals. Following the ischemic period, hearts were reperfused (15 min Langendorff, 20 min working) before assessment of the recovery of function. Ischemic durations (selected to result in approximately 55%-70% recovery in the single-dose group at each temperature) were 1, 10, or 18 h at 37 degrees, 20 degrees, and 10 degrees C. At 37 degrees C, there was a positive correlation between postischemic recovery and the number of infusions during the ischemic period. However, at 20 degrees or 10 degrees C the relationship was reversed and recovery was depressed with increasing number of infusions.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Detrimental effects of multidose hypothermic cardioplegia in the neonatal heart: the role of the frequency of cardioplegic infusions. 205 51

The duration of ischemia resulting in 50% post-ischemic recovery of hemodynamic functions was 25 min in the control isolated working rat hearts and increased to 45 min in the hearts subjected to normothermic cardioplegia plus normothermic global ischemia (36 degrees C) and to 180 min in the hearts subjected to hypothermic cardioplegia and hypothermic ischemia (22 degrees C). Addition of 10(-6) M trifluoperazine to the normothermic St. Thomas' cardioplegic solution considerably improved the protective properties of the solution as assessed by the functional recovery of the heart. Under conditions of hypothermic ischemic arrest the drug failed to improve the protective properties of cardioplegic solution, suggesting a common modality between hypothermia and trifluoperazine-induced protection.
 ...
PMID:Temperature-dependence of the effect of trifluoperazine as a protective agent during cardioplegia in the isolated working rat heart. 208 Sep 4


1 2 3 4 5 6 7 8 9 10 Next >>