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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immature myocardium has a greater tolerance for ischemia than does the mature heart. The effect of ischemia when combined with hypothermia on the newborn heart is poorly understood but has important clinical applications. This study examined the metabolic and functional recovery after 90 minutes of global ischemia at 20 degrees C in neonatal (1 week), immature (1 month), and mature (4 month) isolated working rabbit hearts. Following ischemia, aortic flow, cardiac output, heart rate, and stroke work remained at baseline values for neonatal hearts. Only coronary flow was significantly reduced from a control level of 4.5 +/- 1.4 (standard error of the mean) to 3.3 +/- 1.1 ml/min, p less than 0.05. In the immature group, hemodynamic parameters were below baseline, although no statistical differences were noted. Among mature hearts, however, all hemodynamic values were significantly below preischemic control. Water content was significantly higher in immature (73.2% +/- 1.4%) and mature (75.3% +/- 2.5%) hearts when compared with the neonatal group (46.8% +/- 4.6%), p less than 0.001. Coronary sinus creatine kinase was unchanged from baseline at 10 and 30 minutes following ischemia in the neonatal group. Although demonstrating substantial increases from baseline, statistical significance was not seen in the immature group because of the wide variation about the mean. In the mature group, creatine kinase rose significantly from preischemic levels of 15.4 +/- 4.3 IU/L/gm to 184.2 +/- 51.6 IU/L/gm at 10 minutes (p less than 0.01) and 123.7 +/- 31.9 IU/L/gm at 30 minutes (p less than 0.05). This study demonstrated improved tolerance to prolonged hypothermic ischemia in neonatal rabbit hearts when compared with older hearts subjected to the same conditions. The role of cardioplegic solutions in protecting the neonatal heart during cardiac operations when deep hypothermia is used may be of lesser importance than in the older patient.
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PMID:Recovery of left ventricular function after hypothermic global ischemia. Age-related differences in the isolated working rabbit heart. 394 54

The protective effects of cardioplegic solutions (CS) containing creatine phosphate (CP) were studied in a rat heart model of cardiopulmonary bypass and ischemic cardiac arrest. Isolated rat hearts were subjected to a 3-minute coronary infusion with CS containing CP in normothermic (37 degrees C) and hypothermic (4-6 degrees C) regimes. In the normothermia group, the postischemic functional recovery was 70-75% of the preischemic control value, while the cellular ATP and CP content was reduced but insignificantly. By contrast, in the hypothermia group, the postischemic functional recovery was markedly depressed, with the tissue high-energy phosphate content being appreciably lowered. The data obtained confirm high efficacy of CP-containing cardioplegic solutions administered under normothermia conditions.
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PMID:[Effectiveness of protecting the myocardium against ischemia with a normothermic cardioplegic solution and creatine phosphate]. 396 61

The ability of nifedipine, verapamil, and diltiazem to enhance cardioplegic protection has been assessed using an isolated rat heart preparation as a model of cardiopulmonary bypass and ischemic arrest. With normothermic ischemia (30 or 35 min at 37 degrees C), the addition of these compounds enhanced the protective properties of the St. Thomas' cardioplegic solution. All these compounds showed bell-shaped dose-response characteristics, with the optimal concentrations in terms of functional recovery and enzyme leakage of verapamil being 1.0 mumole/liter; nifedipine, 0.075 mumole/liter; and diltiazem, 0.5 mumole/liter. However, under conditions of hypothermia (150 or 180 min at 20 degrees C), none of these compounds improved postischemic functional recovery, although there was some reduction in enzyme leakage. From these results, further experiments were undertaken to investigate the relationship between calcium antagonists and temperature. Verapamil improved functional recovery at 34, 31 and 29 degrees C, but not at 27, 25, and 20 degrees C. These results suggest a common site of action between hypothermia and calcium antagonists in promoting functional recovery after ischemia.
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PMID:Calcium antagonists and myocardial protection during cardioplegic arrest. 399 50

This study was undertaken to assess the effects of hypothermia and chemical cardioplegia on the functional recovery of hypertrophied non-failing rat hearts subjected to an extended period of global ischaemia. Left ventricular hypertrophy was produced by constriction of the abdominal aorta. Hearts were studied an average of 8 weeks following this procedure. Sham-operated animals served as controls. Twenty-nine isolated isovolumic perfused rat heart preparations were then subjected to 2 h of ischaemic arrest at 15-18 degrees C followed by 45 min of normothermic reperfusion. In one series of hearts (8 sham, 8 hypertrophied), myocardial protection consisted of hypothermia alone. In another series (6 sham, 7 hypertrophied), repeated infusions of cardioplegic solution at 30-min intervals throughout arrest were added to hypothermia. Hypothermia alone resulted in a similar preservation of contractility as evidenced by the recovery of dp/dtmax/left ventricular (LV) systolic pressure after 45 min of reperfusion (91.6 +/- 5.9% of control values in sham vs 78.6 +/- 6.5% in hypertrophied hearts). Conversely, the recovery of compliance was much more impaired in hypertrophied hearts as indicated by a significantly higher percentage of increase in post-ischaemic LV diastolic pressure (DP) (at 45 min of reperfusion: 243.8 +/- 27.5% of control values vs 167.1 +/- 23.8% in sham, P less than 0.05). The addition of cardioplegia improved the preservation of contractility in both groups but its major effect was to normalize the recovery of compliance in hypertrophied hearts so that post-ischaemic LVDP values were no longer different from those recorded in normal hearts (at 45 min of reperfusion: 102.1 +/- 32.8% vs 98.5 +/- 14.2% of pre-ischaemic values respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protective effects of cardioplegia on diastolic function of hypertrophied rat hearts after hypothermic ischaemic arrest. 624

The light and electron microscopic morphology of 57 cadaver renal allografts was assessed at the time of procurement and again after revascularization. Twenty-two kidneys (39%) did not function immediately after transplantation and 19 of these (86%) contained morphologic evidence of acute tubular necrosis (ATN) in the procurement biopsy. The morphology of the post-transplant biopsy was abnormal in all 22 kidneys with delayed function. There was a wide spectrum of morphologic change between the time of procurement and revascularization in all kidneys with normal function. These changes were mild in nature, were usually confined to proximal tubules, and were of unknown clinical significance. The morphology of kidneys that were damaged by the time of procurement was surprisingly different after storage with simple hypothermia (ice) than after storage with hypothermic pulsatile perfusion. The changes attributed to ice storage included endothelial swelling and vacuolation with obliteration and collapse of capillary lumens, fracture and splitting of peritubular basement membrane, and hyalinization of the renal interstitium. It was unknown whether these morphologic abnormalities were associated with delayed recovery of function of the injured kidneys.
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PMID:Renal allograft acute tubular necrosis. II. A light and electron microscopic study of biopsies taken at procurement and after revascularization. 634 15

An isolated working rat heart preparation was used to determine the effect of diltiazem, a calcium antagonist, on the myocardial metabolism and functional recovery in the ischemic and reperfused heart, under conditions of 15 degrees C of topical hypothermia. The hearts were divided into two groups according to the solution injected into aortic root at the onset of ischemia. Group I (25 hearts) were given 3 ml of cold Krebs-Henseleit bicarbonate buffer solution (KHB), and Group II (25 hearts) were given the same dose of KHB containing 300 micrograms of diltiazem. After 30 min of reperfusion following 120 min of ischemia, cardiac output (ml/min) was significantly better in Group II (24.1 +/- 3.2) than in Group I (9.5 +/- 2.5). There were no differences between the groups with regard to tissue levels of creatine phosphate, adenosine triphosphate (ATP), total adenine nucleotide (TAN), glucose-6-phosphate and lactate during the ischemia. However, ATP and TAN levels were significantly higher in Group II after 30 min of reperfusion. These data show that, although diltiazem has little effect in preventing the catabolism of high-energy phosphates during hypothermic ischemia, there was an improvement in myocardial metabolism and an enhanced functional recovery during reperfusion in the diltiazem-treated hearts.
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PMID:Effect of diltiazem on functional recovery and myocardial metabolism during hypothermic global ischemia and normothermic reperfusion. 663 97

Using an isolated rat heart preparation under both aerobic and ischemic conditions we have characterized the temperature dependency of the slow calcium channel-blocking drug verapamil. In the first series of studies, isolated working rat hearts were subjected to global ischemia at 37 degrees, 34 degrees, 31 degrees, 29 degrees, 27 degrees, 25 degrees, and 20 degrees C. The duration of ischemic arrest was adjusted so that in the control group the postischemic recovery of function (aortic flow) was approximately 50% of its preischemic value. Ischemic times were therefore 35, 50, 55, 60, 80, 100, and 130 min, respectively. In all cases hearts were subjected to 3 min preischemic infusion with St. Thomas' cardioplegic solution with or without added verapamil (1.1 mumol/liter). At 37 degrees C verapamil increased recovery by 36.6 +/- 4.8%; this increased to 57.4 +/- 6.0% at 34 degrees C. Below 34 degrees C, however, additional protection was progressively lost, so that at 27 degrees C or below verapamil contributed no significant additional protection. In separate aerobic perfusion studies with paced Langendorff-prepared hearts with intraventricular balloons, verapamil (0.2 mumol/liter) was shown to depress pressure development by up to 76% at 37 degrees C; this increased to 92% at 34 degrees C, but thereafter the drug's negative inotropic effects declined, so that at 24 degrees C and below there was no significant difference in developed pressure between the control and drug-treated groups. On the basis of these and other studies, the argument is advanced that by some mechanism common to both hypothermia and verapamil, the anti-ischemic and negative inotropic effects of verapamil are rendered redundant under conditions of hypothermia.
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PMID:Calcium antagonists and hypothermia: the temperature dependency of the negative inotropic and anti-ischemic properties of verapamil in the isolated rat heart. 674 70

Previous studies from this laboratory utilized mass spectrometry to measure myocardial oxygen (PO2) and carbon dioxide (PCO2) tensions in isolated feline hearts subjected to periods of global ischemia and reperfusion. Myocardial carbon dioxide tension was found to increase during ischemia, and its rate of increase was found to correlate inversely with subsequent recovery of myocardial function following reflow. The present study utilized phosphorus-31 nuclear magnetic resonance (NMR) to assess whether the severity of intracellular acidosis or the depletion of high energy phosphate stores would show a similar correlation with recovery of function. Hyperkalemic cardioplegia employed as a myocardial preservation technqiue in combination with hypothermia was compared with hypothermia alone as the control intervention. The experimental results demonstrated that intracellular pH fell to 6.09 +/- 0.13 with hypothermia alone and to 6.31 +/- 0.09 with cardioplegia plus hypothermia. Furthermore, myocardial ATP content fell to 22% +/- 2% of control with hypothermia alone, while falling to 36% +/- 4% of control with the combined therapy. Recovery of myocardial performance was found to correlate inversely with the severity of intracellular acidosis and depletion of ATP during ischemia. In contrast, no relationship was observed between preservation of phosphoryl-creatinine levels either during ischemia or after reflow and recovery of ventricular function. These results suggest that, similar to mass spectrometry, which allows monitoring of myocardial PCO2, 31P NMR permits the on-line monitoring of intracellular pH as well as high energy phosphate compounds, and thereby provides useful metabolic indices of the severity of ischemia. Since tight coupling was found between changes in these parameters and subsequent recovery of contractile performance, further development of 31P NMR for evaluation of techniques designed to minimize the severity of ischemic damage would seem indicated.
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PMID:Mass spectrometry and phosphorus-31 nuclear magnetic resonance demonstrate additive myocardial protection by potassium cardioplegia and hypothermia during global ischemia. 677 61

Phosphorus-31 nuclear magnetic resonance (31P NMR) can estimate tissue intracellular pH as well as the content of high-energy phosphate metabolites in isolated perfused hearts. We used 31P NMR to examine mechanisms associated with the recovery of ventricular function in hearts subjected to global ischemia and reperfusion, with special emphasis on intracellular pH, a previously unreported variable. Single-dose and multiple-dose administration of a hyperkalemic cardioplegic solution were compared with hypothermia alone in 18 isolated perfused rabbit hearts. Hearts in group 1 were subjected to 24 degrees C hypothermia during 60 minutes of global ischemia; group 2 hearts received a single injection of 37-mM KCL cardioplegic solution at 10 degrees C at the onset of ischemia; and group 3 hearts received a similar initial cardioplegic injection followed by two subsequent 24 degrees C injections at 20-minute intervals during the ischemic period. Using an intraventricular balloon, maximal dP/dt provided a quantitative index of left ventricular performance before and after ischemia. Return of ventricular function expressed as a percentage of control was 54 +/- 11% for group 1, 84 +/- 6% for group 2, and 101 +/- 18% for group 3. Differences in the rate of development of intracellular acidosis were noted during the 60-minute ischemic period. Intracellular pH fell to 6.09 +/- 0.12 in group 1, 6.31 +/- 0.09 in group 2, an 6.79 +/- 0.03 in group 3. In all three groups intracellular pH returned to control (pH 7.20) within 10 minutes of reflow. The metabolic correlates of functional recovery appeared to be the tissue content of ATP at the end of ischemia and after reflow. ATP content at the end of ischemia was 22 +/- 2% of control in group 1 hearts, 31 +/- 4% in group 2 and 64 +/- 2% in group 3. After 45 minutes of reperfusion, ATP levels recovered to 33 +/- 9% of control in group 1, to 71 +/- 9% in group 2 and to 86 +/- 6% in group 3. Although there were no differences between groups in the content of creatine phosphate after 60 minutes of ischemia, the rates of creatine phosphate decline were dissimilar. Further, during the early reflow period, a marked overshoot in tissue creatine phosphate was detected, especially in groups 1 and 2. Histologic damage assessed by light microscopy correlated with the metabolic data, confirming that multidose cardioplegia provided the best preservation of cellular morphology. These results demonstrate that the magnitude of intracellular acidosis and the associated increase in inorganic phosphate correlate inversely with recovery of postischemic ventricular structure and function. ATP, but not creatine phosphate, content correlates with return of contractile performance after reperfusion. The overshoot in creatine phosphate during early reperfusion might impede optimal restoration of ATP content and, as a result, optimal recovery of cell functions.
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PMID:Mechanisms of ischemic myocardial cell damage assessed by phosphorus-31 nuclear magnetic resonance. 679 21

Hypothermic potassium cardioplegia is now commonly used to protect the myocardium during surgically induced ischemia. Because the potassium-related membrane depolarization has been shown to increase calcium influx, we undertook this study to define the effects of varying the calcium content in hyperkalemic perfusates and the effects of using magnesium instead of or in addition to potassium as the arresting agent on the ability of hearts to recover normal function after ischemic arrest. We subjected isolated perfused working rat hearts to 60 minutes of cardioplegic arrest followed by 30 minutes of reperfusion, and measured high-energy phosphate levels every 2 1/2 minutes by phosphorus-31 nuclear magnetic resonance spectroscopy. These data were correlated with postischemic recovery of function. Our results show that potassium cardioplegia may be harmful when the calcium concentration is greater than 1 mM. The kalemic injury is significantly reduced when the calcium content is lowered to 0.25 mM and the greatest extent of preservation is provided by a calcium-poor perfusate (0.25 mM) containing 13 mM magnesium. The beneficial effects of magnesium are not enhanced by subsequent addition of potassium. Close correlations were found between all observed metabolic changes during arrest and the degree of recovery of contractile performance after reperfusion. We conclude that the ability of the myocardium to maintain or resynthesize high-energy phosphate after cardioplegic arrest may be an important determinant of postischemic mechanical performance. These results show that phosphorus-31 nuclear magnetic resonance spectroscopy is a valuable method for evaluating interventions to reduce the severity of ischemic damage.
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PMID:Evaluation of high-energy phosphate metabolism during cardioplegic arrest and reperfusion: a phosphorus-31 nuclear magnetic resonance study. 685 Oct 24


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