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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experiments were conducted to test the hypothesis that the previously demonstrated depression in ventricular function of rats with hyperdynamic sepsis was a result of depressed high energy phosphate levels or altered myocardial substrate utilization. Rats were inoculated with a pooled fecal homogenate, and 48 hr later their hearts were removed and studied using the Langendorff preparation. The coronaries were perfused with a hydrostatic pressure of 90 mmHg, and hearts were paced at 310-320 beats/min. Substrate oxidation was determined by supplying 14C-labeled glucose, lactate, or palmitate in physiologic concentrations, ie, 5.5, 1, and 0.6 mM, respectively. Hearts were frozen either in situ or after 40-50 min of perfusion for the determination of tissue metabolite levels. Myocardial content of high energy phosphates, total adenine nucleotides, and creatine were similar in septic animals and time-matched controls both in situ and after perfusion. Oxidation of exogenous substrates accounted for the total myocardial O2 consumption in both groups of perfused hearts. Palmitate oxidation was responsible for approximately 50% of the total O2 consumption of the heart, with glucose accounting for approximately 20% and lactate for the remainder. The percentage contribution of the three substrates to oxidative metabolism was similar in hearts from septic and time-matched controls; therefore, myocardial substrate preference was not altered by sustained sepsis. These studies also indicate that ischemia and the concomitant fall in high energy phosphates do not contribute to the myocardial dysfunction of hyperdynamic sepsis.
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PMID:Substrate utilization and high energy phosphate levels of hearts from hyperdynamic septic rats. 369 11

Streptozocin-diabetic rats were treated with a combination of triiodothyronine and carnitine for 6 weeks. These compounds were used as they are known to correct the diabetes-induced depression of cardiac myosin ATPase and sarcoplasmic reticular (SR) calcium uptake, respectively. Myocardial performance, which was assessed using the working heart preparation, revealed a depression of function in untreated diabetics when compared with controls at most left atrial filling pressures. Hearts from diabetic rats treated with the combination exhibited depression at only the higher filling pressures as compared with untreated or treated controls. The results suggest that functional alterations occurring as a result of diabetes cannot be accounted for by the depression of cardiac myosin ATPase and SR calcium uptake alone.
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PMID:Effects of triiodothyronine and carnitine therapy on myocardial dysfunction in diabetic rats. 375 16

The reviewed studies support the contention that during the high flow or hyperdynamic phase of gram-negative septicemia, cardiac reserve is compromised because of intrinsic myocardial dysfunction. The latter is not referable to coronary hypoperfusion or peripheral pooling or decreased venous return. Although, under resting, nonstressed conditions, indices of myocardial function may appear normal or even elevated, a decreased reserve is evident when additional stress is imposed on the myocardium. Hearts removed from septic rats during the hyperdynamic stage and perfused in vitro (using the isolated perfused working heart preparation) showed a rightward and downward shift in work function curves, indicating a severe depression in cardiac function. Possible mechanisms for the observed dysfunction are discussed. No significant alterations in high energy phosphate production or substrate utilization were observed, indicating that altered myocardial metabolism is not likely to be a significant contributor to the dysfunction. Our results suggest that cardiac dysfunction is partially due to an elevation in the cytosolic calcium concentration which may slow the rate of ventricular relaxation. These studies emphasize that intrinsic cardiac function is depressed early during the course of the septic episode at a time that precedes the onset of circulatory shock.
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PMID:The effect of hyperdynamic sepsis on myocardial performance. 399 94

The efficacy of moderate hypothermia with rewarming in attenuating the myocardial and circulatory consequences of acute coronary ligation was studied in open-chest, anesthetized dogs. Thirty minutes after ligation of the proximal left anterior descending coronary artery, 14 dogs were surface-cooled to 27 degrees C, maintained at this temperature for 2 hr, rewarmed to normothermic levels, and monitored for an additional hour. Fifteen dogs were maintained for a corresponding time period after coronary ligation at normothermic levels. Dogs maintained normothermic demonstrated significant depression (from preligation values) of dP/dt, cardiac output (CO), stroke volume (SV), and left ventricular stroke work and power (LVSW, LVSP) at elevated levels of left ventricular end-diastolic pressure (LVEDP). Dogs subjected to the hypothermic procedure demonstrated decreased inotropic status during hypothermia, but with rewarming, exhibited significantly greater values of left ventricular pressure, dP/dt, CO, SV, LVSW, and LVSP at lower values of LVEDP than observed in dogs maintained normothermic. Increased dysrhythmic activity was not observed during hypothermia. Hearts from dogs subjected to the hypothermic protocol demonstrated qualitatively greater dehydrogenase activity both at the periphery and in the center of the nonperfused region. The results suggest that moderate hypothermia during evolving myocardial infarction may preserve left ventricular cardio- and hemodynamics and thus may be useful in delaying morphological and functional deterioration until definitive treatment can be instituted.
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PMID:Salutary effects of moderate hypothermia on the circulatory and myocardial consequences of acute coronary occlusion in dogs. 407 11

Isolated perfused hearts from diabetic rats exhibit a decreased responsiveness to increasing work loads. However, the precise time point at which functional alterations occur is not clearly established. Previous observations in our laboratory have suggested that the alterations in myocardial function are not apparent at 30 days whereas they are clearly seen 100 days after streptozotocin-induced diabetes. We studied the cardiac function of 6-week diabetic rats using the isolated perfused heart preparation. The 6-week time period was found to be sufficient to cause depression of myocardial function in these animals. We also studied the effect of insulin treatment on myocardial performance of diabetic rats. Insulin treatment was initiated 3 days and 6 weeks after injection of streptozotocin (STZ). The treatment was continued for 6 and 4 weeks in the respective groups. Hearts from 6-week diabetic animals exhibited a depressed left ventricular developed pressure (LVDP) and positive and negative dP/dt at higher filling pressures when compared with 6-week control animals. However, the depression was not seen in the 6-week insulin-treated diabetic animals. Ten-week diabetic rat hearts also showed a depression of LVDP and positive and negative dP/dt when compared with 10-week controls. The group of animals that had been diabetic for 6 weeks and then treated for 4 weeks with insulin exhibited a reversal of the depressed myocardial function. These results demonstrate that depression of myocardial performance, which is evident 6 weeks after diabetes is induced, can be prevented if insulin treatment is initiated as the disease is induced. Further, insulin treatment is capable of reversing the abnormalities after they have occurred.
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PMID:Prevention and reversal of altered myocardial function in diabetic rats by insulin treatment. 634 59

An alteration in calcium metabolism in cardiac muscle was observed in diabetic rats 3 mo after streptozotocin treatment. Depression of cardiac output and left ventricular pressure development were more sensitive to decreased extra-cellular calcium in hearts from diabetic than from control animals and occurred within the normal physiological range of freely ionized serum calcium. This decrease in calcium sensitivity was not present after 2 wk of diabetes. In vivo treatment with insulin for 1 mo completely reversed the effect. Addition of octanoate (0.3 mM) to the perfusate of isolated hearts completely reversed the defect, whereas epinephrine (25 nM) only partially reversed it. When the glucose concentration of the perfusate was decreased, the function of diabetic hearts declined and was further diminished at decreasing calcium levels. Hearts from normal rats were unaffected. These results suggest that there is a defect in calcium metabolism or flux in the chronic diabetic rat heart.
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PMID:Altered sensitivity of chronic diabetic rat heart to calcium. 636 27

The ischemic state of the myocardium of the isolated working rat heart after induction of normothermic ischemic cardiac arrest was assessed by the interrelationship among changes in myocardial ultrastructure, mitochondrial oxidative phosphorylation, and tissue high energy phosphate contents. At all time intervals (10-40 minutes) studied, the ultrastructural changes were more severe in the subendocardium than in the subepicardium. After 25-40 minutes of normothermic ischemic cardiac arrest, the mitochondrial oxygen uptake (state 3) became increasingly depressed, particularly in mitochondria isolated from the subendocardium. Mitochondrial oxidative function, as measured in vitro, did not correlate well with mitochondrial ultrastructural damage. In addition, the effects of coronary reperfusion on the ability of the ischemic heart to recover in terms of ultrastructure, mechanical, and metabolic function were evaluated. Hearts subjected to 10-40 minutes of normothermic ischemic cardiac arrest showed almost complete ultrastructural recovery of the subepicardium upon reperfusion; regression of ultrastructural changes occurred to a lesser extent in the subendocardium. Reperfusion for 30 minutes did not alleviate the depression in mitochondrial oxidative function, while tissue ATP levels did not return to control, preischemic levels. After 20 minutes of normothermic ischemic cardiac arrest, the mechanical performance of the working heart during reperfusion was significantly depressed, compared with pre-ischemic control values. Normal ultrastructure of the subendocardium always accompanied mechanical recovery, while improvement of mitochondrial oxidative function was not essential.
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PMID:Normothermic ischemic cardiac arrest of the isolated working rat heart. Effects of time and reperfusion on myocardial ultrastructure, mitochondrial oxidative function, and mechanical recovery. 662 16

Hearts were excised from 30 male Sprague-Dawley rats and perfused in a modified Langendorff system to examine the interactions of fentanyl and diazepam on myocardial contractility as measured by left ventricular dP/dtmax. Various concentrations of fentanyl and diazepam were added to the nonrecirculating 37 degrees C perfusate to determine ED25 and ED50 for depression of dP/dtmax. Combinations of fentanyl and diazepam at a fixed negative inotropic potency ratio of 1:1 were used to determine the ED25 and ED50 of this combination. Isobolographic analyses performed at ED25 and ED50 revealed that the negative inotropic interaction of fentanyl and diazepam is purely additive. It is unlikely that a supraadditive negative inotropic effect can explain the supraadditive hemodynamic depression reported in humans when diazepam and fentanyl are combined; perhaps systemic vascular effects of this drug combination account for the clinical drug interactions.
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PMID:Additive negative inotropic effect of a combination of diazepam and fentanyl. 669 89

Gram-negative sepsis causes a depression of the myocardium such that ventricular function curves generated on isolated perfused hearts removed from septic rats are displaced downward and to the right of control. Alcohol consumption can also cause a depression of the myocardium, especially if the period of alcohol feeding is prolonged. However, even before overt changes in the myocardium can be measured as a result of alcohol consumption, chronic alcoholism can result in a potentiation of sepsis-induced cardiac depression (Am. J. Physiol. 250:H1857-H1863, 1991). The purpose of the present study was to determine if 1 week of withdrawal of alcohol from the diet after 8 weeks of alcohol consumption would reverse the potentiation by alcohol of sepsis-induced cardiac depression. Animals were fed an ethanol-containing diet in which ethanol contributed 36% of the total calories. Rats were fed this diet or a control liquid diet for 8 weeks, and then some animals were taken off the alcohol diet and placed on the control diet for 1 week. Sepsis was induced in control-fed, alcohol-fed or withdrawal animals by the administration of Escherichia coli into the dorsal subcutaneous space. Nonseptic animals received sterile saline in this space. The following day animals were anesthetized, and the hearts were removed and studied as isolated working hearts. Hearts removed from septic and alcohol septic animals showed severe depression of cardiac contractile performance. Hearts from the withdrawal group, however, were less compromised by sepsis and showed only a few signs of cardiac dysfunction. Withdrawal from alcohol for 1 week thus resulted in protection of the heart from sepsis-induced cardiac depression.
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PMID:1-week withdrawal from 8 weeks alcohol consumption protects the heart from sepsis-induced dysfunction. 748 27

Ischemia causes significant damage to the heart as manifested by decreases in ventricular performance. Several different methods have been shown to protect the heart from ischemic injury--one is operative over a short period (an hour) and the other over longer periods (a day). The latter form of protection has been demonstrated in rats after induction of Gram-negative sepsis or administration of endotoxin or cytokines. In the present study we determined whether guinea pigs would also show induction of cardiac protection subsequent to a dose of endotoxin. Male guinea pigs were injected with 1 mg of endotoxin and studied the following day. Hearts were perfused at a constant perfusion pressure and studied in an isovolumic mode. Left ventricular developed pressure was significantly lower in the endotoxin-treated group than in the control group. After 35 min of total ischemia and 25 min of reperfusion, recovery of left ventricular developed pressure was complete in the endotoxin group but significantly decreased in the control group such that after ischemia and reperfusion, there was no significant difference in left ventricular performance between the two groups. Coronary flow was significantly greater in the endotoxin group than in the control group both prior to and after ischemia. Hearts from endotoxin-treated guinea pigs resumed spontaneous contractile activity sooner and released less lactate upon reperfusion than did the control group. Thus prior treatment of guinea pigs with endotoxin resulted in depression of the isolated heart but also resulted in protection of the isolated heart from further damage due to ischemia/reperfusion injury.
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PMID:Effects of endotoxin on the guinea pig heart response to ischemia reperfusion injury. 749 99


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